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  • 1. Order onlineBuy this publication >>
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.

    The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.

    Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.

    We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.

    List of papers
    1. An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons
    Open this publication in new window or tab >>An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons
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    2010 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, no 4, p. 1069-1082Article in journal (Refereed) Published
    Abstract [en]

    Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.

    Place, publisher, year, edition, pages
    Ios Press, 2010
    Keywords
    Alzheimers disease; differentiation; in vitro model; neuroblastoma; tau
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-58227 (URN)10.3233/JAD-2010-091363 (DOI)000279539500012 ()
    Note
    Original Publication: Lotta Agholme, Tobias Lindström, Katarina Kågedal, Jan Marcusson and Martin Hallbeck, An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons, 2010, Journal of Alzheimer's Disease, (20), 4, 1069-1082. http://dx.doi.org/10.3233/JAD-2010-091363 Copyright: Ios Press http://www.iospress.nl/ Available from: 2010-08-10 Created: 2010-08-09 Last updated: 2019-10-14
    2. Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease
    Open this publication in new window or tab >>Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease
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    2014 (English)In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 58, p. 29-39Article in journal (Refereed) Published
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-81339 (URN)10.1016/j.mcn.2013.11.001 (DOI)000331853600004 ()
    Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2019-10-14Bibliographically approved
    3. Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy
    Open this publication in new window or tab >>Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy
    Show others...
    2012 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, no 2, p. 343-358Article in journal (Refereed) Published
    Abstract [en]

    The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.

    Place, publisher, year, edition, pages
    I O S Press, 2012
    Keywords
    AβPP processing, Alzheimer’s disease, amyloid- peptide, autophagy, cell death, LC-3, lysosome, p70S6K, proteasome
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81340 (URN)10.3233/JAD-2012-120001 (DOI)000307377300011 ()22555375 (PubMedID)
    Note

    funding agencies|foundations of Engqvist, Wiberg, Hedlund, Osterman, and Stohne||Gustav V and Queen Victorias Foundation||Swedish Alzheimers foundation||Ostergotland County Council||Swedish Research Council||

    Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2019-10-14Bibliographically approved
    4. Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid
    Open this publication in new window or tab >>Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid
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    2012 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, no 26, p. 8767-8777Article in journal (Refereed) Published
    Abstract [en]

    Alzheimers disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of beta-amyloid (A beta) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble A beta oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric A beta. Additional studies conducted in a human donor-acceptor cell model show that this A beta transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular A beta oligomers play a role in neurodegeneration, and they explain the manner in which A beta can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.

    Place, publisher, year, edition, pages
    SOC NEUROSCIENCE, 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-79695 (URN)10.1523/JNEUROSCI.0615-12.2012 (DOI)000305890700003 ()
    Available from: 2012-08-13 Created: 2012-08-13 Last updated: 2019-10-14
    Download full text (pdf)
    The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease
    Download (pdf)
    omslag
  • 2.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Benedikz, Eirikur
    Department of Neurobiology, Division of Neurodegeneration, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy2012In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, no 2, p. 343-358Article in journal (Refereed)
    Abstract [en]

    The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.

  • 3.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Geriatrics.
    Lindström, Tobias
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, no 4, p. 1069-1082Article in journal (Refereed)
    Abstract [en]

    Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.

    Download full text (pdf)
    FULLTEXT01
  • 4. Order onlineBuy this publication >>
    Bjartmar, Lisa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Pharmacological and Developmental Aspects on Neuronal Plasticity2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neuronal plasticity means the ability of the brain, its cells and networks to adapt and adjust to new challenges, a process which is ongoing throughout life. The goal of this thesis was to gain better understanding of the molecular events that follow different types of stimulations of brain structures such as the hippocampus, a key region for cognitive functions with overriding control on the corticosteroid system. A better knowledge of the mechanisms involved in neuronal plasticity is fundamental in the development of strategies for improving health in patients suffering from major depression or cognitive disorders such as Alzheimer’s disease.

    Antidepressant drugs induce the expression of several genes involved in neuronal plasticity, a mechanism which may explain the several weeks time lag between treatment initiation and clinical effect commonly observed in patients. Besides, there are indications that disturbances in the corticosteroid system are involved in the pathogenesis of major depression. Therefore, the mRNA expression of the glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) as well as of the immediate-early genes NGFI-A and NGFI-B was analyzed using in situ hybridization in the hippocampus and cortex after 21 days treatment with various antidepressant drugs having different monoaminergic profiles. The mRNA expression of the transcription factors was selectively increased depending on region and also on the monoaminergic profile of the drug given. Generally, drugs with less specificity for monoamines had an overall more anatomically wide-spread inducible effect.

    In a follow-up study the message expression of the synaptic protein NP2 was investigated in a similar setting where long-term (21 days) was compared with short-term (3 days) antidepressant treatment. In addition to the hippocampus, the medial habenula, a relay station within the limbic system was analyzed. Overall there was an upregulation of NP2 mRNA expression following long-term treatment irrespective of the monoaminergic profile of the drug. Simultaneously, NP2 mRNA was analyzed in rats exposed to enriched, normal or deprived environments respectively, an experimental setting known to affect neuronal plasticity. However, in contrast to the pharmacological treatment, this environmental stimulation did not lead to alterations in NP2 mRNA expression in any of the regions studied.

    Finally, the function of NP2 as well as the closely related proteins NP1 and NPR was investigated. The “knock-out mouse” technique was used to eliminate these neuronal pentraxins (NPs), both individually and in various combinations. Since previous data had suggested that the NPs are involved in synaptic development, axonal refinement in the visual system during development was analyzed in these animals. In the NP1/NP2 knock-out mice, synaptic formation, axonal development and refinement occurred at a significantly slower rate than in wild-type mice, indicating that the NPs may be necessary for activity-dependent synaptogenesis.

    In conclusion, the results of the studies constituting this thesis demonstrate that long-term treatment with antidepressant drugs, possessing different monoaminergic profiles, has selective effects on the expression of NGFI-A, NGFI-B, GR and MR in the mammalian brain. In general, the least selective drugs exhibit the most profound effect suggesting that induction of neuronal plasticity is more effective with multiple neuronal inputs. The results also show that NP2 expression is induced by antidepressant drugs, in contrast to environmental stimulation, supporting the presence of different pathways for inducing neuronal plasticity depending on type of stimuli. Finally, this thesis indicates that the neuronal pentraxins play an important part in synaptic development.

     

    List of papers
    1. Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats
    Open this publication in new window or tab >>Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats
    Show others...
    1998 (English)In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 62, no 1, p. 92-95Article in journal (Refereed) Published
    Abstract [en]

    Adult male rats were treated with the antidepressant drug amitriptyline for 21 days and the expression of specific transcription factors was examined. NGFI-A mRNA expression was increased in the hippocampus and in the cerebral cortex. MR mRNA was increased in the hippocampus while GR mRNA was increased in selective hippocampal regions. There was no change in the NGFI-B mRNA expression. Thus, NGFI-A may be a mediator of plasticity-related phenomena induced by antidepressant drugs.

    Place, publisher, year, edition, pages
    Elsevier Science B.V., 1998
    Keywords
    NGFI-A, glucocorticoid receptor, antidepressant, hippocampus, transcription factor
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51403 (URN)10.1016/S0169-328X(98)00243-5 (DOI)
    Available from: 2009-10-30 Created: 2009-10-30 Last updated: 2017-12-12Bibliographically approved
    2. Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat
    Open this publication in new window or tab >>Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat
    Show others...
    2000 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 151, no 1, p. 7-12Article in journal (Refereed) Published
    Abstract [en]

    There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase), with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27674 (URN)10.1007/s002130000468 (DOI)12412 (Local ID)12412 (Archive number)12412 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Neuronal pentraxins mediate synaptic refinement in the developing visual system
    Open this publication in new window or tab >>Neuronal pentraxins mediate synaptic refinement in the developing visual system
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    2006 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 26, no 23, p. 6269-6281Article in journal (Refereed) Published
    Abstract [en]

    Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar to that of wild-type mice, but several other parameters of retinal activity were altered. RGCs cultured from these mice exhibited a significant delay in functional maturation of glutamatergic synapses. Other developmental processes, such as pathfinding of RGCs at the optic chiasm and hippocampal long-term potentiation and long-term depression, appeared normal in NP-deficient mice. These data indicate that NPs are necessary for early synaptic refinements in the mammalian retina and dorsal lateral geniculate nucleus. We speculate that NPs exert their effects through mechanisms that parallel the known role of short pentraxins outside the CNS.

    Keywords
    retinogeniculate, neuronal pentraxins, synaptic plasticity, LTP, long-term potentiation, LTD, long-term depression, development, knock-out, retinal ganglion cell
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51407 (URN)10.1523/JNEUROSCI.4212-05.2006 (DOI)
    Available from: 2009-10-30 Created: 2009-10-30 Last updated: 2018-07-03Bibliographically approved
    4. Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula
    Open this publication in new window or tab >>Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula
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    2010 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1328, p. 24-33Article in journal (Refereed) Published
    Abstract [en]

    Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, is involved in activity-dependent synaptogenesis and synaptic plasticity. In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. This study demonstrates that NP2 mRNA is robustly expressed in the hippocampus and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is enhanced in the hippocampal subregions as well as in the MHb after long-term treatment with antidepressant drugs of various monoaminergic profiles, indicating a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant induced plasticity, but not EE induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.

    Place, publisher, year, edition, pages
    Elsevier, 2010
    Keywords
    Neuronal pentraxins, narp, habenula, hippocampus, synaptic plasticity, antidepressant
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51408 (URN)10.1016/j.brainres.2010.03.004 (DOI)000277682400003 ()
    Note
    On the day of the defence day the status of this article was: Submitted.Available from: 2009-10-30 Created: 2009-10-30 Last updated: 2019-10-14Bibliographically approved
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    Pharmacological and Developmental Aspects on Neuronal Plasticity
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    Cover
  • 5.
    Bjartmar, Lisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Alkhori, Liza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ruud, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology.
    Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula2010In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1328, p. 24-33Article in journal (Refereed)
    Abstract [en]

    Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, is involved in activity-dependent synaptogenesis and synaptic plasticity. In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. This study demonstrates that NP2 mRNA is robustly expressed in the hippocampus and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is enhanced in the hippocampal subregions as well as in the MHb after long-term treatment with antidepressant drugs of various monoaminergic profiles, indicating a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant induced plasticity, but not EE induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.

  • 6.
    Carlsson, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Olsson, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Reis, Margareta
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Wålinder, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Nordin, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Lundmark, Jöns
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Scordo, M. G.
    Dahl, M-L.
    Bengtsson, Finn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Enantioselective Analysis of Citalopram and Metabolites in Adolescents2001In: Therapeutic drug monitoring, ISSN 0163-4356, Vol. 23, no 6, p. 658-664Article in journal (Refereed)
    Abstract [en]

    Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.

  • 7.
    Cuervo, Ana Maria
    et al.
    Albert Einstein College of Medicine.
    Bergamini, Ettore
    University of Pisa.
    Brunk, Ulf
    Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
    Droge, Wolf
    Heidelberg, Germany.
    Ffrench, Martine
    Central Hospital, Lyon.
    Terman, Alexei
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Autophagy and aging - The importance of maintaining "clean" cells2005In: autophagy, Vol. 1, no 3, p. 131-140Article, review/survey (Refereed)
    Abstract [en]

    A decrease in the turnover of cellular components and the intracellular accumulation of altered macromolecules and organelles are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. In this work we review the molecular defects responsible for the malfunctioning of two forms of autophagy, macroautophagy and chaperone-mediated outophagy, in old mammals, and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. These and other possible experimental restorative efforts are discussed.

  • 8.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Granerus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Hannestad, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Ljungdahl, Å.
    Department of Neurology, Huddinge Hospital, Stockholm.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma1999In: Acta neurologica Scandinavica, ISSN 0001-6314, Vol. 100, no 4, p. 231-237Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients.

    METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time.

    RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy.

    CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.

  • 9.
    Dong, Huan-Ji
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Unosson, Mitra
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health Consequences Associated with Being Overweight or Obese: A Swedish Population-Based Study of 85-Year-Olds2012In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, no 2, p. 243-250Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine whether being overweight or obese is associated with significant health outcomes in an 85-year-old population. less thanbrgreater than less thanbrgreater thanDESIGN: A cross-sectional population-based study. less thanbrgreater than less thanbrgreater thanSETTING: Linkoping, Sweden. less thanbrgreater than less thanbrgreater thanPARTICIPANTS: Three hundred thirty-eight people born in 1922 were identified using the local authoritys register. less thanbrgreater than less thanbrgreater thanMEASUREMENTS: Data related to sociodemographic characteristics, health-related quality of life (HRQoL), assistance use, and the presence of diseases were collected using a postal questionnaire. Anthropometry and functional status were assessed during home and geriatric clinic visits. Diseases were double-checked in the electronic medical records, and information about health service consumption was obtained from the local healthcare register. less thanbrgreater than less thanbrgreater thanRESULTS: Overweight (body mass index (BMI) 25.0-29.9 kg/m(2)) and obese (BMI andgt;= 30.0 kg/m(2)) participants perceived more difficulty performing instrumental activities of daily living (IADLs) and had more comorbidity than their normal-weight counterparts (BMI 18.5-24.9 kg/m(2)), but their overall HRQoL and health service costs did not differ from those of normal-weight participants. After controlling for sociodemographic factors, being overweight did not influence IADLs or any comorbidity, but obese participants were more likely to perceive greater difficulty in performing outdoor activities (odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.1-4) and cleaning (OR = 2.2, 95% CI = 1.2-4.2) than their normal-weight counterparts. Although obesity was also associated with multimorbidity (OR = 3, 95% CI = 1.2-8), the health service cost of each case of multimorbidity (n = 251) was highest in normalweight participants and nearly three times as much as in obese participants (ratio: 2.9, 95% CI = 1.1-8.1). less thanbrgreater than less thanbrgreater thanCONCLUSION: For 85-year-olds, being obese, as opposed to overweight, is associated with self-reported activity limitations and comorbidities. Overweight older adults living in their own homes in this population had well-being similar to that of those with normal weight.

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  • 10.
    Dong, Huan-Ji
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study2013In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 13, no 120Article in journal (Refereed)
    Abstract [en]

    Background

    As life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population.

    Methods

    Health and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients’ case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models.

    Results

    Cluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1–5.7) and women (OR = 3, 95% CI = 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1–2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR = 1.6, 95% CI = 1–2.4) and one of the women’s aging clusters (OR = 0.5, 95% CI = 0.3–0.8) showed interaction effects on hospitalization.

    Conclusion

    In this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.

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  • 11.
    Eek, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Everyday technology and 86-year-old individuals in Sweden2011In: Disability and Rehabilitation: Assistive Technology, ISSN 1748-3107, E-ISSN 1748-3115, Vol. 2, no 6, p. 123-129Article in journal (Refereed)
    Abstract [en]

    Purpose

    The aim was to investigate everyday technology use in the homes of 86-year-old individuals in Sweden regarding usage, benefits or perceived problems and to study their perception of the technical development and its influence on daily living.

     

    Method

    The design was both quantitative and qualitative. An interview was conducted at a home visit performed by an occupational therapist using a questionnaire including questions on demographics and everyday technology. In addition, a qualitative part was performed based on an interview guide. Two hundred seventy four people participated.

     

    Results

    The results indicate that watching TV was important for almost all 86-year-old individuals. This medium, combined with reading newspapers, was important for obtaining news. The most common problems in usage of everyday technology were related to visual or hearing impairments or operating difficulties. References to the Internet for further information were perceived as problematic for individuals without access to a computer. Another difficulty was automated telephone services. Cognitive deficits impeded everyday technology use and increased perceived problems.

     

    Conclusions

    Access to information and services are important elements in order to be an active participant in the society. Everyday technology is an area that should be addressed by occupational therapists in order to facilitate daily living.

  • 12.
    Fall, Per-Arne
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Aspects of Parkinson's disease. Epidemiology, risk factors and ECT in advanced disease1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose was to investigate some aspects of epidemiology, risk factors and treatment with ECT in advanced Parkinson’s disease (PD).

    In study I, we performed a descriptive epidemiologic population-based survey in the Central Health Care District in Östergötland in south-east Sweden, with a population of almost 150,000 inhabitants 1989. The case finding was accomplished in three ways: 1. Collection of all prescriptions for Parkinson’s disease. 2. Search in medical files. 3. Checking with all nursing homes in the area. The crude prevalence was found to be 115 per 100,000 inhabitants. When we used the European Standard Population as a tool for easy comparisons of PD prevalence between different areas and time periods 76 PD-cases per 100,000 inhabitants were found. The corresponding incidences were 11.0 (crude) and 7.9 (age standardised) per 100,000 person-years. Mean age at onset was 65.6. A low prevalence and a high age at onset suggested that e.g. environmental factors could influence the occurrence of PD, and the results implies that only few such factors were present in the investigated area.

    The findings led to study II, a case-control study which investigated the possible impact of nutritional and environmental risk factors for idiopathic Parkinson’s disease (IP), including 113 cases and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire. No increased risk was found for any of the nutrients. A reduced risk was found for coffee, wine, and spirits but also for broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. These findings could indicate an antioxidant effect. Frequency of preceding and present smoking was reduced in IP patients. Possible mechanisms are discussed. Various occupational groups and exposures were analysed and increased risks of IP in men were found for agricultural work, pesticide exposure, male carpenters, and in female cleaners.

    In advanced PD there is a need for further therapeutic improvements, and electroconvulsive therapy (ECT) is one insufficiently explored and evaluated method. In study III ECT 16 non-depressed, nondemented PD patients with advanced disease were treated with ECT. In all patients an antiparkinsonian effect of ECT was seen, lasting between a few days and 18 months. Five patients, all with signs of blood brain barrier damage, developed transitory mental confusion after ECT. The results indicated that ECT could cause increased dopaminergic activity, which led us to study IV. Single photon emission computed tomography (SPECT) with the cocaine analogue [123I]-β-CIT was used in order to visualise dopaminergic neurones in the brain. Six patients with PD were examined before and after a series of ECT, and in three cases SPECT was also repeated after one year. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with most pronounced symptomatology. No significant change in uptake of [123I]-β-CIT was seen after ECT, although all patients improved and the most pronounced improvement was seen in patients with less advanced PD.

    Study V points at two new positive observations with maintenance ECT (MECT). i.e. repeated ECT treatment of PD. One patient had either severe mental side effects on higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT implied marked improvement in parkinsonian symptoms without mental side effects. Another PD patient, who also had a mental depression, showed slight improvement of motor symptoms on a series of ECT. When treated with MECT further antiparkinsonian effects were seen.

    List of papers
    1. Age standardised incidence and prevalence of Parkinson´s disease in a Swedish community
    Open this publication in new window or tab >>Age standardised incidence and prevalence of Parkinson´s disease in a Swedish community
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    1996 (English)In: Journal of Clinical Epidemiology, ISSN 0895-4356, Vol. 49, no 6, p. 637-641Article in journal (Refereed) Published
    Abstract [en]

    Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low -dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.

    Keywords
    Parkinson's disease, epidemiological study, age standardization, age at onset, male preponderance, low risk
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13530 (URN)10.1016/0895-4356(96)00003-0 (DOI)
    Available from: 1999-05-28 Created: 1999-05-28 Last updated: 2018-10-08
    2. Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden
    Open this publication in new window or tab >>Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden
    1999 (English)In: Movement Disorders, ISSN 0885-3185, Vol. 14, no 1, p. 28-37Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE AND METHODS: To investigate the possible impact of nutritional and environmental risk factors for idiopathic Parkinson's disease (IP), a case-control study was performed in the county of Ostergötland in southeastern Sweden. The study involved 113 cases of IP and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire.

    RESULTS: No increased risk was found for any of the nutritional items in which information was requested. A reduced risk was found for coffee, wine, and liquor at various consumption levels but also for fried or broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. All these food and drink items contain niacin. As in many studies, the frequency of preceding and present smoking was reduced in IP patients. Various occupational groups and exposures were analyzed and increased risks of IP in men were found for agricultural work along with pesticide exposure; this was also the case for male carpenters and female cleaners.

    CONCLUSIONS: The findings indicate that nutritional factors and occupational exposures, especially to pesticides, could be of etiologic importance in IP.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13531 (URN)
    Available from: 1999-05-28 Created: 1999-05-28 Last updated: 2009-08-18
    3. ECT in Parkinson's disease: Changes in motor symptoms, monoamine metabolites and neuropeptides
    Open this publication in new window or tab >>ECT in Parkinson's disease: Changes in motor symptoms, monoamine metabolites and neuropeptides
    Show others...
    1995 (English)In: Journal of Neural Transmission. Parkinson's disease and dementia section., ISSN 0936-3076, Vol. 10, no 2-3, p. 129-140Article in journal (Refereed) Published
    Abstract [en]

    Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13532 (URN)
    Available from: 1999-05-28 Created: 1999-05-28 Last updated: 2009-08-18
    4. ECT in Parkinson's disease-dopamine transporter visualised by [123I]-beta-CIT SPECT
    Open this publication in new window or tab >>ECT in Parkinson's disease-dopamine transporter visualised by [123I]-beta-CIT SPECT
    2000 (English)In: Journal of Neural Transmission, ISSN 0300-9564, Vol. 107, no 8-9, p. 997-1008Article in journal (Refereed) Published
    Abstract [en]

    Parkinson's disease (PD) is characterised by a loss of dopaminergic neurones in the basal ganglia. These neurones may be visualised by single photon emission computed tomography (SPECT) with the cocaine analogue 2β-carboxymethyl-3-β-(4-iodophenyl)tropane ([123I]β-CIT), which labels the dopamine reuptake sites in the nerve terminals. In order to evaluate the possibility to predict the outcome of ECT a prospective study was per-formed with six PD patients in whom the [123I]β-CIT uptake was measured before and after an electroconvulsive therapy (ECT) series. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with the most pronounced symptomathology. No significant change in uptake of the radioligand was seen after ECT. Patients with best uptake and thus with less advanced PD improved most after ECT. The possibility to use the [123I]β-CIT uptake to predict the outcome of ECT treatment has to be further evaluated.

    Keywords
    Parkinson's disease, electroconvulsive therapy, single photon emission computerized tomography (SPECT), [123I]β-CIT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13533 (URN)10.1007/s007020070048 (DOI)
    Available from: 1999-05-28 Created: 1999-05-28 Last updated: 2009-08-18
    5. Maintenance ECT in Parkinson's disease
    Open this publication in new window or tab >>Maintenance ECT in Parkinson's disease
    1999 (English)In: Journal of Neural Transmission, ISSN 0300-9564, Vol. 106, no 7-8, p. 737-741Article in journal (Refereed) Published
    Abstract [en]

    Electroconvulsive therapy (ECT) has an anti-Parkinsonian effect. In two cases repeated single ECT, i.e. maintenance ECT (MECT), caused different, hitherto unreported positive effects. One patient had either severe mental side effects from higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT entailed a marked improvement in parkinsonian symptoms without mental side effects. Another patient with depression as well as Parkinson's disease who showed a slight improvement of motor symptoms after a series of ECT presented further anti-parkinsonian effects on MECT.

    Keywords
    Parkinson's disease, paranoid symptoms, hallucination, maintenance ECT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13534 (URN)10.1007/s007020050194 (DOI)
    Available from: 1999-05-28 Created: 1999-05-28 Last updated: 2009-08-18
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  • 13.
    Fall, Per-Arne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Hansson, Gunilla
    Lindvall, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences.
    Granérus, Ann-Kathrine.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Age standardised incidence and prevalence of Parkinson´s disease in a Swedish community1996In: Journal of Clinical Epidemiology, ISSN 0895-4356, Vol. 49, no 6, p. 637-641Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low -dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.

  • 14.
    Fall, Per-Arne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Ekberg, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Radiation Physics . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Granerus, Ann-Kathrine
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Granerus, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    ECT in Parkinson's disease - dopamine transporter visualised by [I-123]-beta-CIT SPECT2000In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 107, no 8-9, p. 997-1008Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is characterised by a loss of dopaminergic neurones in the basal ganglia. These neurones may be visualised by single photon emission computed tomography (SPECT) with the cocaine analogue 2 beta-carboxymethyl-3-beta-(4-iodophenyl)tropane ([(123)]beta-CIT), which labels the dopamine reuptake sites in the nerve terminals. In order to evaluate the possibility to predict the outcome of ECT a prospective study was performed with six PD patients in whom the [I-123]beta-CIT uptake was measured before and after an electroconvulsive therapy (ECT) series. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with the most pronounced symptomathology. No significant change in uptake of the radioligand was seen after ECT. Patients with best uptake and thus with less advanced PD improved most after ECT. The possibility to use the [I-123]beta-CIT uptake to predict the outcome of ECT treatment has to be further evaluated.

  • 15.
    Fall, Per-Arne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Ekberg, Stefan
    Linköping University, Department of Medicine and Health Sciences, Radiation Physics . Linköping University, Faculty of Health Sciences.
    Granérus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Granérus, Göran
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    ECT in Parkinson's disease-dopamine transporter visualised by [123I]-beta-CIT SPECT2000In: Journal of Neural Transmission, ISSN 0300-9564, Vol. 107, no 8-9, p. 997-1008Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is characterised by a loss of dopaminergic neurones in the basal ganglia. These neurones may be visualised by single photon emission computed tomography (SPECT) with the cocaine analogue 2β-carboxymethyl-3-β-(4-iodophenyl)tropane ([123I]β-CIT), which labels the dopamine reuptake sites in the nerve terminals. In order to evaluate the possibility to predict the outcome of ECT a prospective study was per-formed with six PD patients in whom the [123I]β-CIT uptake was measured before and after an electroconvulsive therapy (ECT) series. The side-to-side difference in the radiotracer uptake was found to be significantly lower in striatum located contralaterally to the part of the body with the most pronounced symptomathology. No significant change in uptake of the radioligand was seen after ECT. Patients with best uptake and thus with less advanced PD improved most after ECT. The possibility to use the [123I]β-CIT uptake to predict the outcome of ECT treatment has to be further evaluated.

  • 16.
    Fall, Per-Arne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Ekman, R.
    Granérus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Linköping University, Faculty of Health Sciences.
    Wålinder, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    ECT in Parkinson's disease: Changes in motor symptoms, monoamine metabolites and neuropeptides1995In: Journal of Neural Transmission. Parkinson's disease and dementia section., ISSN 0936-3076, Vol. 10, no 2-3, p. 129-140Article in journal (Refereed)
    Abstract [en]

    Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.

  • 17.
    Fall, Per-Arne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Axelson, Olav
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Granérus, Ann-Kathrine.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden1999In: Movement Disorders, ISSN 0885-3185, Vol. 14, no 1, p. 28-37Article in journal (Refereed)
    Abstract [en]

    PURPOSE AND METHODS: To investigate the possible impact of nutritional and environmental risk factors for idiopathic Parkinson's disease (IP), a case-control study was performed in the county of Ostergötland in southeastern Sweden. The study involved 113 cases of IP and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire.

    RESULTS: No increased risk was found for any of the nutritional items in which information was requested. A reduced risk was found for coffee, wine, and liquor at various consumption levels but also for fried or broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. All these food and drink items contain niacin. As in many studies, the frequency of preceding and present smoking was reduced in IP patients. Various occupational groups and exposures were analyzed and increased risks of IP in men were found for agricultural work along with pesticide exposure; this was also the case for male carpenters and female cleaners.

    CONCLUSIONS: The findings indicate that nutritional factors and occupational exposures, especially to pesticides, could be of etiologic importance in IP.

  • 18.
    Fall, Per-Arne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Granérus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Maintenance ECT in Parkinson's disease1999In: Journal of Neural Transmission, ISSN 0300-9564, Vol. 106, no 7-8, p. 737-741Article in journal (Refereed)
    Abstract [en]

    Electroconvulsive therapy (ECT) has an anti-Parkinsonian effect. In two cases repeated single ECT, i.e. maintenance ECT (MECT), caused different, hitherto unreported positive effects. One patient had either severe mental side effects from higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT entailed a marked improvement in parkinsonian symptoms without mental side effects. Another patient with depression as well as Parkinson's disease who showed a slight improvement of motor symptoms after a series of ECT presented further anti-parkinsonian effects on MECT.

  • 19. Garcia, J.
    et al.
    Ahmadi, Ahmad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Wonnacott, A.
    University of Wales, College of Medicine, Cardiff, United Kingdom.
    Sutcliffe, W.
    University of Wales, College of Medicine, Cardiff, United Kingdom.
    Nagga, K.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Association of insulin-like growth factor-1 receptor polymorphism in dementia2006In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 22, no 5-6, p. 439-444Article in journal (Refereed)
    Abstract [en]

    There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1-2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females. Copyright © 2006 S. Karger AG.

  • 20.
    Johansson, Inga-Maj
    et al.
    Department of Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden.
    Bjartmar, Lisa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Ross, Svante
    Astra Arcus, Södertälje, Sweden.
    Seckl, Jonathan
    Department of Medicine, Western General Hospital, Edinburgh, Scotland, UK.
    Olsson, Tommy
    Department of Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden.
    Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats1998In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 62, no 1, p. 92-95Article in journal (Refereed)
    Abstract [en]

    Adult male rats were treated with the antidepressant drug amitriptyline for 21 days and the expression of specific transcription factors was examined. NGFI-A mRNA expression was increased in the hippocampus and in the cerebral cortex. MR mRNA was increased in the hippocampus while GR mRNA was increased in selective hippocampal regions. There was no change in the NGFI-B mRNA expression. Thus, NGFI-A may be a mediator of plasticity-related phenomena induced by antidepressant drugs.

  • 21.
    Johansson, Maria M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Validation of the Neurobehavioral Cognitive Status Examination and the Rivermead Behavioural Memory Test in investigations of dementia2012In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, Vol. 19, no 3, p. 282-287Article in journal (Refereed)
    Abstract [en]

    The aim of this retrospective study was to validate two commonly used instruments, Cognistat and the Rivermead Behavioural Memory Test, RBMT, for detection of MCI and mild dementia. Two different diagnosis groups, mild cognitive impairment (MCI) and Alzheimer's disease combined with mixed dementia representing mild dementia (MD), were compared with a group of patients who did not receive a diagnosis of dementia. All patients were assessed at a specialized outpatient memory clinic in a university hospital in Sweden using the Mini Mental State Examination (MMSE), Cognistat, and RBMT. Sensitivity, specificity, predictive value, and likelihood ratio were calculated for the tests. The Cognistat and RBMT have moderate validity in the detection of MCI and mild dementia. On their own, none of the tests used is sufficient for diagnosing MCI or mild dementia. A combination of the Cognistat and RBMT provides additional information in early stage dementia; in this regard the RBMT is better than the Cognistat, which also has other limitations. The RBMT can be helpful for distinguishing between MCI and mild dementia. There is a need for a more sensitive screening test to capture early cognitive impairment related to patients' occupational performance and problems in daily life.

  • 22.
    Johansson, Maria M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Cognition, daily living, and health-related quality of life in 85-year-olds in Sweden2012In: Aging, Neuropsychology and Cognition, ISSN 1382-5585, E-ISSN 1744-4128, Vol. 19, no 3, p. 421-432Article in journal (Refereed)
    Abstract [en]

    This study investigates how cognition influences activities of daily living and health-related quality of life in 85-year-olds in Sweden (n = 373). Data collection included a postal questionnaire comprising demographics and health-related quality of life measured by the EQ-5D. The ability to perform personal activities of daily living (PADL) was assessed during a home visit that included administering the Mini Mental State Examination (MMSE). Cognitive impairment was shown in 108 individuals (29%). The majority were independent with respect to PADL. A larger number of participants with cognitive impairment reported that they needed assistance in instrumental activities of daily living (IADL) compared to the group without cognitive impairment. Impaired cognition was significantly related to problems with IADL. Significant but low correlations were found between cognition and health-related quality of life – higher ratings on perceived quality of life correlated with higher results on the MMSE.

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  • 23.
    Järemo, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, East County Primary Health Care.
    Buller, Caroline
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Winblad, Bengt
    Department of Neurobiology, Care Sciences and Society (NVS), KI-Alzheimer’s Disease Research Center, Karolinska Institute, Huddinge; Sweden.
    Alzheimer's disease is characterized by more low-density erythrocytes with increased volume and enhanced β-amyloid x-40 content2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 5, p. 489-492Article in journal (Other academic)
  • 24.
    Kalldalen, Anette
    et al.
    Jonköping University.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Nagga, Katarina
    Lund University.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Occupational Performance Problems in 85-Year-Old Women and Men in Sweden2012In: OTJR (Thorofare, N.J.), ISSN 1539-4492, E-ISSN 1938-2383, Vol. 32, no 2, p. 30-38Article in journal (Refereed)
    Abstract [en]

    An area of concern for occupational therapy is to increase preventive interventions among relatively healthy elderly individuals. The purpose of this study was to explore occupational performance problems among 85-year-old women and men in relation to demographic data, mental health, and health-related quality of life. Participants completed a postal questionnaire including the EuroQoL health-related quality of life measurement. Instruments used during a home visit were the Canadian Occupational Performance Measure, the Mini-Mental State Examination, and the Geriatric Depression scale. The sample comprised 380 individuals. Women experienced poorer health and more occupational performance problems in community management, household management, and quiet leisure than men. Impaired cognitive function, lower self-rated health, and higher risk of depression correlated with a larger number of occupational performance problems. Intervention planning should be based on individual perceptions of meaningful occupations and environmental considerations.

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  • 25.
    Karlsson, Thomas
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Mårdh, Selina
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Emotion and recollective experience in Alzheimer’s diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Emotional changes are common in Alzheimer’s disease (AD). In addition, damage to brain regions involved in emotion is abundant in AD. Although these finding imply that emotion memory is severely compromised in AD, absolute or relative sparing of emotional memory has occasionally been reported. Hence, we wanted to clarify how well AD patients can remember emotion words. Eighteen AD patients and fifteen healthy older persons participated in the experiment. Participants studied neutral, positive, and negative words. Implicit and explicit memory was assessed in two tasks: a word-fragment completion task and a recognition task, respectively. In the latter task, participants were asked to provide recollective judgments when they indicated that they recognized a word from previous study. Results indicated that AD patients responded to valence, and in particular negative valence, similar to controls, that AD patients evidenced severe deficits as to recollective experience, and that implicit memory remained intact in AD.

  • 26.
    Kim, Woojin Scott
    et al.
    Prince of Wales Medical Research Institute, Randwick NSW, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney NSW, Australia.
    Bhatia, Surabhi
    Prince of Wales Medical Research Institute, Randwick NSW, Australia.
    Elliott, David A
    Prince of Wales Medical Research Institute, Randwick NSW, Australia.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Geriatrics.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    McCann, Heather
    Prince of Wales Medical Research Institute, Randwick NSW, Australia.
    Halliday, Glenda M
    Prince of Wales Medical Research Institute, Randwick NSW, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney NSW, Australia.
    Barnham, Kevin J
    Department of Pathology, University of Melbourne, VIC, Australia.
    Garner, Brett
    Prince of Wales Medical Research Institute, Randwick NSW, Australia; School of Biological Sciences, Faculty of Science, University of Wollongong, Wollongong NSW, Australia.
    Increased ATP-binding cassette transporter A1 expression in Alzheimer's disease hippocampal neurons2010In: Journal of Alzheimer's disease : JAD, ISSN 1875-8908, Vol. 21, no 1, p. 193-205Article in journal (Refereed)
    Abstract [en]

    ATP-binding cassette transporter A1 (ABCA1) reduces amyloid-beta burden in transgenic mouse models of Alzheimer's disease (AD). Associations between ABCA1 polymorphisms and AD risk are also established. Little is known regarding the regulation of ABCA1 expression in the brain and how this may be affected by AD. In the present study we assessed ABCA1 mRNA and protein expression in the hippocampus of AD cases compared to controls. ABCA1 was clearly expressed in hippocampal neurons and expression was increased two- to three-fold in AD cases. The increased hippocampal ABCA1 expression was associated with increased APOE and PUMA gene expression, implying an association with neuronal stress. Consistent with this, treatment of SK-N-SH neurons with amyloid-beta peptide resulted in a 48% loss in survival and a significant upregulation of ABCA1, APOE, and PUMA gene expression. Studies in young (2 month) and old (12 month) transgenic mice expressing a familial AD form of human amyloid-beta protein precursor and presenilin-1 revealed a significant age-dependent upregulation of hippocampal Abca1 compared to wild-type control mice. However, hippocampal Apoe and Puma gene expression were not correlated with increased Abca1 expression in mice. Our data indicate that ABCA1 is upregulated in AD hippocampal neurons potentially via an amyloid-beta-mediated pathway.

  • 27.
    Klionsky, Daniel J
    et al.
    Life Sciences Institute; Department of Molecular, Cellular and Developmental Biology; Department of Biological Chemistry; University of Michigan; Ann Arbor, MI, USA .
    Abdalla, Fabio C
    Laboratory of Structural and Functional Biology; Federal University of São Carlos (UFSCar); Campus Sorocaba; São Paulo State, Brazil .
    Abeliovich, Hagai
    Department of Biochemistry and Food Science; Hebrew University; Rehovot, Israel .
    Abraham, Robert T
    Acevedo-Arozena, Abraham
    Adeli, Khosrow
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Agnello, Maria
    Agostinis, Patrizia
    Aguirre-Ghiso, Julio A
    Ahn, Hyung Jun
    Ait-Mohamed, Ouardia
    Ait-Si-Ali, Slimane
    Akematsu, Takahiko
    Akira, Shizuo
    Al-Younes, Hesham M
    Al-Zeer, Munir A
    Albert, Matthew L
    Albin, Roger L
    Alegre-Abarrategui, Javier
    Aleo, Maria Francesca
    Alirezaei, Mehrdad
    Almasan, Alexandru
    Almonte-Becerril, Maylin
    Amano, Atsuo
    Amaravadi, Ravi
    Amarnath, Shoba
    Amer, Amal O
    Andrieu-Abadie, Nathalie
    Anantharam, Vellareddy
    Ann, David K
    Anoopkumar-Dukie, Shailendra
    Aoki, Hiroshi
    Apostolova, Nadezda
    Auberger, Patrick
    Baba, Misuzu
    Backues, Steven K
    Baehrecke, Eric H
    Bahr, Ben A
    Bai, Xue-Yuan
    Bailly, Yannick
    Baiocchi, Robert
    Baldini, Giulia
    Balduini, Walter
    Ballabio, Andrea
    Bamber, Bruce A
    Bampton, Edward T W
    Bánhegyi, Gábor
    Bartholomew, Clinton R
    Bassham, Diane C
    Bast, Robert C
    Batoko, Henri
    Bay, Boon-Huat
    Beau, Isabelle
    Béchet, Daniel M
    Begley, Thomas J
    Behl, Christian
    Behrends, Christian
    Bekri, Soumeya
    Bellaire, Bryan
    Bendall, Linda J
    Benetti, Luca
    Berliocchi, Laura
    Bernardi, Henri
    Bernassola, Francesca
    Besteiro, Sébastien
    Bhatia-Kissova, Ingrid
    Bi, Xiaoning
    Biard-Piechaczyk, Martine
    Blum, Janice S
    Boise, Lawrence H
    Bonaldo, Paolo
    Boone, David L
    Bornhauser, Beat C
    Bortoluci, Karina R
    Bossis, Ioannis
    Bost, Frédéric
    Bourquin, Jean-Pierre
    Boya, Patricia
    Boyer-Guittaut, Michaël
    Bozhkov, Peter V
    Brady, Nathan R
    Brancolini, Claudio
    Brech, Andreas
    Brenman, Jay E
    Brennand, Ana
    Bresnick, Emery H
    Brest, Patrick
    Bridges, Dave
    Bristol, Molly L
    Brookes, Paul S
    Brown, Eric J
    Brumell, John H
    Brunetti-Pierri, Nicola
    Brunk, Ulf T
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bulman, Dennis E
    Bultman, Scott J
    Bultynck, Geert
    Burbulla, Lena F
    Bursch, Wilfried
    Butchar, Jonathan P
    Buzgariu, Wanda
    Bydlowski, Sergio P
    Cadwell, Ken
    Cahová, Monika
    Cai, Dongsheng
    Cai, Jiyang
    Cai, Qian
    Calabretta, Bruno
    Calvo-Garrido, Javier
    Camougrand, Nadine
    Campanella, Michelangelo
    Campos-Salinas, Jenny
    Candi, Eleonora
    Cao, Lizhi
    Caplan, Allan B
    Carding, Simon R
    Cardoso, Sandra M
    Carew, Jennifer S
    Carlin, Cathleen R
    Carmignac, Virginie
    Carneiro, Leticia A M
    Carra, Serena
    Caruso, Rosario A
    Casari, Giorgio
    Casas, Caty
    Castino, Roberta
    Cebollero, Eduardo
    Cecconi, Francesco
    Celli, Jean
    Chaachouay, Hassan
    Chae, Han-Jung
    Chai, Chee-Yin
    Chan, David C
    Chan, Edmond Y
    Chang, Raymond Chuen-Chung
    Che, Chi-Ming
    Chen, Ching-Chow
    Chen, Guang-Chao
    Chen, Guo-Qiang
    Chen, Min
    Chen, Quan
    Chen, Steve S-L
    Chen, WenLi
    Chen, Xi
    Chen, Xiangmei
    Chen, Xiequn
    Chen, Ye-Guang
    Chen, Yingyu
    Chen, Yongqiang
    Chen, Yu-Jen
    Chen, Zhixiang
    Cheng, Alan
    Cheng, Christopher H K
    Cheng, Yan
    Cheong, Heesun
    Cheong, Jae-Ho
    Cherry, Sara
    Chess-Williams, Russ
    Cheung, Zelda H
    Chevet, Eric
    Chiang, Hui-Ling
    Chiarelli, Roberto
    Chiba, Tomoki
    Chin, Lih-Shen
    Chiou, Shih-Hwa
    Chisari, Francis V
    Cho, Chi Hin
    Cho, Dong-Hyung
    Choi, Augustine M K
    Choi, DooSeok
    Choi, Kyeong Sook
    Choi, Mary E
    Chouaib, Salem
    Choubey, Divaker
    Choubey, Vinay
    Chu, Charleen T
    Chuang, Tsung-Hsien
    Chueh, Sheau-Huei
    Chun, Taehoon
    Chwae, Yong-Joon
    Chye, Mee-Len
    Ciarcia, Roberto
    Ciriolo, Maria R
    Clague, Michael J
    Clark, Robert S B
    Clarke, Peter G H
    Clarke, Robert
    Codogno, Patrice
    Coller, Hilary A
    Colombo, María I
    Comincini, Sergio
    Condello, Maria
    Condorelli, Fabrizio
    Cookson, Mark R
    Coombs, Graham H
    Coppens, Isabelle
    Corbalan, Ramon
    Cossart, Pascale
    Costelli, Paola
    Costes, Safia
    Coto-Montes, Ana
    Couve, Eduardo
    Coxon, Fraser P
    Cregg, James M
    Crespo, José L
    Cronjé, Marianne J
    Cuervo, Ana Maria
    Cullen, Joseph J
    Czaja, Mark J
    D'Amelio, Marcello
    Darfeuille-Michaud, Arlette
    Davids, Lester M
    Davies, Faith E
    De Felici, Massimo
    de Groot, John F
    de Haan, Cornelis A M
    De Martino, Luisa
    De Milito, Angelo
    De Tata, Vincenzo
    Debnath, Jayanta
    Degterev, Alexei
    Dehay, Benjamin
    Delbridge, Lea M D
    Demarchi, Francesca
    Deng, Yi Zhen
    Dengjel, Jörn
    Dent, Paul
    Denton, Donna
    Deretic, Vojo
    Desai, Shyamal D
    Devenish, Rodney J
    Di Gioacchino, Mario
    Di Paolo, Gilbert
    Di Pietro, Chiara
    Díaz-Araya, Guillermo
    Díaz-Laviada, Inés
    Diaz-Meco, Maria T
    Diaz-Nido, Javier
    Dikic, Ivan
    Dinesh-Kumar, Savithramma P
    Ding, Wen-Xing
    Distelhorst, Clark W
    Diwan, Abhinav
    Djavaheri-Mergny, Mojgan
    Dokudovskaya, Svetlana
    Dong, Zheng
    Dorsey, Frank C
    Dosenko, Victor
    Dowling, James J
    Doxsey, Stephen
    Dreux, Marlène
    Drew, Mark E
    Duan, Qiuhong
    Duchosal, Michel A
    Duff, Karen
    Dugail, Isabelle
    Durbeej, Madeleine
    Duszenko, Michael
    Edelstein, Charles L
    Edinger, Aimee L
    Egea, Gustavo
    Eichinger, Ludwig
    Eissa, N Tony
    Ekmekcioglu, Suhendan
    El-Deiry, Wafik S
    Elazar, Zvulun
    Elgendy, Mohamed
    Ellerby, Lisa M
    Eng, Kai Er
    Engelbrecht, Anna-Mart
    Engelender, Simone
    Erenpreisa, Jekaterina
    Escalante, Ricardo
    Esclatine, Audrey
    Eskelinen, Eeva-Liisa
    Espert, Lucile
    Espina, Virginia
    Fan, Huizhou
    Fan, Jia
    Fan, Qi-Wen
    Fan, Zhen
    Fang, Shengyun
    Fang, Yongqi
    Fanto, Manolis
    Fanzani, Alessandro
    Farkas, Thomas
    Farré, Jean-Claude
    Faure, Mathias
    Fechheimer, Marcus
    Feng, Carl G
    Feng, Jian
    Feng, Qili
    Feng, Youji
    Fésüs, László
    Feuer, Ralph
    Figueiredo-Pereira, Maria E
    Fimia, Gian Maria
    Fingar, Diane C
    Finkbeiner, Steven
    Finkel, Toren
    Finley, Kim D
    Fiorito, Filomena
    Fisher, Edward A
    Fisher, Paul B
    Flajolet, Marc
    Florez-McClure, Maria L
    Florio, Salvatore
    Fon, Edward A
    Fornai, Francesco
    Fortunato, Franco
    Fotedar, Rati
    Fowler, Daniel H
    Fox, Howard S
    Franco, Rodrigo
    Frankel, Lisa B
    Fransen, Marc
    Fuentes, José M
    Fueyo, Juan
    Fujii, Jun
    Fujisaki, Kozo
    Fujita, Eriko
    Fukuda, Mitsunori
    Furukawa, Ruth H
    Gaestel, Matthias
    Gailly, Philippe
    Gajewska, Malgorzata
    Galliot, Brigitte
    Galy, Vincent
    Ganesh, Subramaniam
    Ganetzky, Barry
    Ganley, Ian G
    Gao, Fen-Biao
    Gao, George F
    Gao, Jinming
    Garcia, Lorena
    Garcia-Manero, Guillermo
    Garcia-Marcos, Mikel
    Garmyn, Marjan
    Gartel, Andrei L
    Gatti, Evelina
    Gautel, Mathias
    Gawriluk, Thomas R
    Gegg, Matthew E
    Geng, Jiefei
    Germain, Marc
    Gestwicki, Jason E
    Gewirtz, David A
    Ghavami, Saeid
    Ghosh, Pradipta
    Giammarioli, Anna M
    Giatromanolaki, Alexandra N
    Gibson, Spencer B
    Gilkerson, Robert W
    Ginger, Michael L
    Goncu, Ebru
    Gongora, Céline
    Gonzalez, Claudio D
    Gonzalez, Ramon
    González-Estévez, Cristina
    González-Polo, Rosa Ana
    Gonzalez-Rey, Elena
    Gorbunov, Nikolai V
    Gorski, Sharon
    Goruppi, Sandro
    Gottlieb, Roberta A
    Gozuacik, Devrim
    Granato, Giovanna Elvira
    Grant, Gary D
    Green, Kim N
    Gregorc, Aleš
    Gros, Frédéric
    Grose, Charles
    Grunt, Thomas W
    Gual, Philippe
    Guan, Jun-Lin
    Guan, Kun-Liang
    Guichard, Sylvie M
    Gukovskaya, Anna S
    Gukovsky, Ilya
    Gunst, Jan
    Gustafsson, Asa B
    Halayko, Andrew J
    Hale, Amber N
    Halonen, Sandra K
    Hamasaki, Maho
    Han, Feng
    Han, Ting
    Hancock, Michael K
    Hansen, Malene
    Harada, Hisashi
    Harada, Masaru
    Hardt, Stefan E
    Harper, J Wade
    Harris, Adrian L
    Harris, James
    Harris, Steven D
    Hébert, Marie-Joseé
    Heidenreich, Kim A
    Helfrich, Miep H
    Helgason, Gudmundur V
    Henske, Elizabeth P
    Herman, Brian
    Herman, Paul K
    Hetz, Claudio
    Hilfiker, Sabine
    Hill, Joseph A
    Hocking, Lynne J
    Hofman, Paul
    Hofmann, Thomas G
    Höhfeld, Jörg
    Holyoake, Tessa L
    Hong, Ming-Huang
    Hood, David A
    Hotamisligil, Gökhan S
    Houwerzijl, Ewout J
    Høyer-Hansen, Maria
    Hu, Bingren
    Hu, Chien-An A
    Hu, Hong-Ming
    Hua, Ya
    Huang, Canhua
    Huang, Ju
    Huang, Shengbing
    Huang, Wei-Pang
    Huber, Tobias B
    Huh, Won-Ki
    Hung, Tai-Ho
    Hupp, Ted R
    Hur, Gang Min
    Hurley, James B
    Hussain, Sabah N A
    Hussey, Patrick J
    Hwang, Jung Jin
    Hwang, Seungmin
    Ichihara, Atsuhiro
    Ilkhanizadeh, Shirin
    Inoki, Ken
    Into, Takeshi
    Iovane, Valentina
    Iovanna, Juan L
    Ip, Nancy Y
    Isaka, Yoshitaka
    Ishida, Hiroyuki
    Isidoro, Ciro
    Isobe, Ken-ichi
    Iwasaki, Akiko
    Izquierdo, Marta
    Izumi, Yotaro
    Jaakkola, Panu M
    Jäättelä, Marja
    Jackson, George R
    Jackson, William T
    Janji, Bassam
    Jendrach, Marina
    Jeon, Ju-Hong
    Jeung, Eui-Bae
    Jiang, Hong
    Jiang, Hongchi
    Jiang, Jean X
    Jiang, Ming
    Jiang, Qing
    Jiang, Xuejun
    Jiang, Xuejun
    Jiménez, Alberto
    Jin, Meiyan
    Jin, Shengkan
    Joe, Cheol O
    Johansen, Terje
    Johnson, Daniel E
    Johnson, Gail V W
    Jones, Nicola L
    Joseph, Bertrand
    Joseph, Suresh K
    Joubert, Annie M
    Juhász, Gábor
    Juillerat-Jeanneret, Lucienne
    Jung, Chang Hwa
    Jung, Yong-Keun
    Kaarniranta, Kai
    Kaasik, Allen
    Kabuta, Tomohiro
    Kadowaki, Motoni
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Kamada, Yoshiaki
    Kaminskyy, Vitaliy O
    Kampinga, Harm H
    Kanamori, Hiromitsu
    Kang, Chanhee
    Kang, Khong Bee
    Kang, Kwang Il
    Kang, Rui
    Kang, Yoon-A
    Kanki, Tomotake
    Kanneganti, Thirumala-Devi
    Kanno, Haruo
    Kanthasamy, Anumantha G
    Kanthasamy, Arthi
    Karantza, Vassiliki
    Kaushal, Gur P
    Kaushik, Susmita
    Kawazoe, Yoshinori
    Ke, Po-Yuan
    Kehrl, John H
    Kelekar, Ameeta
    Kerkhoff, Claus
    Kessel, David H
    Khalil, Hany
    Kiel, Jan A K W
    Kiger, Amy A
    Kihara, Akio
    Kim, Deok Ryong
    Kim, Do-Hyung
    Kim, Dong-Hou
    Kim, Eun-Kyoung
    Kim, Hyung-Ryong
    Kim, Jae-Sung
    Kim, Jeong Hun
    Kim, Jin Cheon
    Kim, John K
    Kim, Peter K
    Kim, Seong Who
    Kim, Yong-Sun
    Kim, Yonghyun
    Kimchi, Adi
    Kimmelman, Alec C
    King, Jason S
    Kinsella, Timothy J
    Kirkin, Vladimir
    Kirshenbaum, Lorrie A
    Kitamoto, Katsuhiko
    Kitazato, Kaio
    Klein, Ludger
    Klimecki, Walter T
    Klucken, Jochen
    Knecht, Erwin
    Ko, Ben C B
    Koch, Jan C
    Koga, Hiroshi
    Koh, Jae-Young
    Koh, Young Ho
    Koike, Masato
    Komatsu, Masaaki
    Kominami, Eiki
    Kong, Hee Jeong
    Kong, Wei-Jia
    Korolchuk, Viktor I
    Kotake, Yaichiro
    Koukourakis, Michael I
    Kouri Flores, Juan B
    Kovács, Attila L
    Kraft, Claudine
    Krainc, Dimitri
    Krämer, Helmut
    Kretz-Remy, Carole
    Krichevsky, Anna M
    Kroemer, Guido
    Krüger, Rejko
    Krut, Oleg
    Ktistakis, Nicholas T
    Kuan, Chia-Yi
    Kucharczyk, Roza
    Kumar, Ashok
    Kumar, Raj
    Kumar, Sharad
    Kundu, Mondira
    Kung, Hsing-Jien
    Kurz, Tino
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Kwon, Ho Jeong
    La Spada, Albert R
    Lafont, Frank
    Lamark, Trond
    Landry, Jacques
    Lane, Jon D
    Lapaquette, Pierre
    Laporte, Jocelyn F
    László, Lajos
    Lavandero, Sergio
    Lavoie, Josée N
    Layfield, Robert
    Lazo, Pedro A
    Le, Weidong
    Le Cam, Laurent
    Ledbetter, Daniel J
    Lee, Alvin J X
    Lee, Byung-Wan
    Lee, Gyun Min
    Lee, Jongdae
    Lee, Ju-Hyun
    Lee, Michael
    Lee, Myung-Shik
    Lee, Sug Hyung
    Leeuwenburgh, Christiaan
    Legembre, Patrick
    Legouis, Renaud
    Lehmann, Michael
    Lei, Huan-Yao
    Lei, Qun-Ying
    Leib, David A
    Leiro, José
    Lemasters, John J
    Lemoine, Antoinette
    Lesniak, Maciej S
    Lev, Dina
    Levenson, Victor V
    Levine, Beth
    Levy, Efrat
    Li, Faqiang
    Li, Jun-Lin
    Li, Lian
    Li, Sheng
    Li, Weijie
    Li, Xue-Jun
    Li, Yan-bo
    Li, Yi-Ping
    Liang, Chengyu
    Liang, Qiangrong
    Liao, Yung-Feng
    Liberski, Pawel P
    Lieberman, Andrew
    Lim, Hyunjung J
    Lim, Kah-Leong
    Lim, Kyu
    Lin, Chiou-Feng
    Lin, Fu-Cheng
    Lin, Jian
    Lin, Jiandie D
    Lin, Kui
    Lin, Wan-Wan
    Lin, Weei-Chin
    Lin, Yi-Ling
    Linden, Rafael
    Lingor, Paul
    Lippincott-Schwartz, Jennifer
    Lisanti, Michael P
    Liton, Paloma B
    Liu, Bo
    Liu, Chun-Feng
    Liu, Kaiyu
    Liu, Leyuan
    Liu, Qiong A
    Liu, Wei
    Liu, Young-Chau
    Liu, Yule
    Lockshin, Richard A
    Lok, Chun-Nam
    Lonial, Sagar
    Loos, Benjamin
    Lopez-Berestein, Gabriel
    López-Otín, Carlos
    Lossi, Laura
    Lotze, Michael T
    Lőw, Peter
    Lu, Binfeng
    Lu, Bingwei
    Lu, Bo
    Lu, Zhen
    Luciano, Frédéric
    Lukacs, Nicholas W
    Lund, Anders H
    Lynch-Day, Melinda A
    Ma, Yong
    Macian, Fernando
    MacKeigan, Jeff P
    Macleod, Kay F
    Madeo, Frank
    Maiuri, Luigi
    Maiuri, Maria Chiara
    Malagoli, Davide
    Malicdan, May Christine V
    Malorni, Walter
    Man, Na
    Mandelkow, Eva-Maria
    Manon, Stéphen
    Manov, Irena
    Mao, Kai
    Mao, Xiang
    Mao, Zixu
    Marambaud, Philippe
    Marazziti, Daniela
    Marcel, Yves L
    Marchbank, Katie
    Marchetti, Piero
    Marciniak, Stefan J
    Marcondes, Mateus
    Mardi, Mohsen
    Marfe, Gabriella
    Mariño, Guillermo
    Markaki, Maria
    Marten, Mark R
    Martin, Seamus J
    Martinand-Mari, Camille
    Martinet, Wim
    Martinez-Vicente, Marta
    Masini, Matilde
    Matarrese, Paola
    Matsuo, Saburo
    Matteoni, Raffaele
    Mayer, Andreas
    Mazure, Nathalie M
    McConkey, David J
    McConnell, Melanie J
    McDermott, Catherine
    McDonald, Christine
    McInerney, Gerald M
    McKenna, Sharon L
    McLaughlin, BethAnn
    McLean, Pamela J
    McMaster, Christopher R
    McQuibban, G Angus
    Meijer, Alfred J
    Meisler, Miriam H
    Meléndez, Alicia
    Melia, Thomas J
    Melino, Gerry
    Mena, Maria A
    Menendez, Javier A
    Menna-Barreto, Rubem F S
    Menon, Manoj B
    Menzies, Fiona M
    Mercer, Carol A
    Merighi, Adalberto
    Merry, Diane E
    Meschini, Stefania
    Meyer, Christian G
    Meyer, Thomas F
    Miao, Chao-Yu
    Miao, Jun-Ying
    Michels, Paul A M
    Michiels, Carine
    Mijaljica, Dalibor
    Milojkovic, Ana
    Minucci, Saverio
    Miracco, Clelia
    Miranti, Cindy K
    Mitroulis, Ioannis
    Miyazawa, Keisuke
    Mizushima, Noboru
    Mograbi, Baharia
    Mohseni, Simin
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Molero, Xavier
    Mollereau, Bertrand
    Mollinedo, Faustino
    Momoi, Takashi
    Monastyrska, Iryna
    Monick, Martha M
    Monteiro, Mervyn J
    Moore, Michael N
    Mora, Rodrigo
    Moreau, Kevin
    Moreira, Paula I
    Moriyasu, Yuji
    Moscat, Jorge
    Mostowy, Serge
    Mottram, Jeremy C
    Motyl, Tomasz
    Moussa, Charbel E-H
    Müller, Sylke
    Muller, Sylviane
    Münger, Karl
    Münz, Christian
    Murphy, Leon O
    Murphy, Maureen E
    Musarò, Antonio
    Mysorekar, Indira
    Nagata, Eiichiro
    Nagata, Kazuhiro
    Nahimana, Aimable
    Nair, Usha
    Nakagawa, Toshiyuki
    Nakahira, Kiichi
    Nakano, Hiroyasu
    Nakatogawa, Hitoshi
    Nanjundan, Meera
    Naqvi, Naweed I
    Narendra, Derek P
    Narita, Masashi
    Navarro, Miguel
    Nawrocki, Steffan T
    Nazarko, Taras Y
    Nemchenko, Andriy
    Netea, Mihai G
    Neufeld, Thomas P
    Ney, Paul A
    Nezis, Ioannis P
    Nguyen, Huu Phuc
    Nie, Daotai
    Nishino, Ichizo
    Nislow, Corey
    Nixon, Ralph A
    Noda, Takeshi
    Noegel, Angelika A
    Nogalska, Anna
    Noguchi, Satoru
    Notterpek, Lucia
    Novak, Ivana
    Nozaki, Tomoyoshi
    Nukina, Nobuyuki
    Nürnberger, Thorsten
    Nyfeler, Beat
    Obara, Keisuke
    Oberley, Terry D
    Oddo, Salvatore
    Ogawa, Michinaga
    Ohashi, Toya
    Okamoto, Koji
    Oleinick, Nancy L
    Oliver, F Javier
    Olsen, Laura J
    Olsson, Stefan
    Opota, Onya
    Osborne, Timothy F
    Ostrander, Gary K
    Otsu, Kinya
    Ou, Jing-hsiung James
    Ouimet, Mireille
    Overholtzer, Michael
    Ozpolat, Bulent
    Paganetti, Paolo
    Pagnini, Ugo
    Pallet, Nicolas
    Palmer, Glen E
    Palumbo, Camilla
    Pan, Tianhong
    Panaretakis, Theocharis
    Pandey, Udai Bhan
    Papackova, Zuzana
    Papassideri, Issidora
    Paris, Irmgard
    Park, Junsoo
    Park, Ohkmae K
    Parys, Jan B
    Parzych, Katherine R
    Patschan, Susann
    Patterson, Cam
    Pattingre, Sophie
    Pawelek, John M
    Peng, Jianxin
    Perlmutter, David H
    Perrotta, Ida
    Perry, George
    Pervaiz, Shazib
    Peter, Matthias
    Peters, Godefridus J
    Petersen, Morten
    Petrovski, Goran
    Phang, James M
    Piacentini, Mauro
    Pierre, Philippe
    Pierrefite-Carle, Valérie
    Pierron, Gérard
    Pinkas-Kramarski, Ronit
    Piras, Antonio
    Piri, Natik
    Platanias, Leonidas C
    Pöggeler, Stefanie
    Poirot, Marc
    Poletti, Angelo
    Poüs, Christian
    Pozuelo-Rubio, Mercedes
    Prætorius-Ibba, Mette
    Prasad, Anil
    Prescott, Mark
    Priault, Muriel
    Produit-Zengaffinen, Nathalie
    Progulske-Fox, Ann
    Proikas-Cezanne, Tassula
    Przedborski, Serge
    Przyklenk, Karin
    Puertollano, Rosa
    Puyal, Julien
    Qian, Shu-Bing
    Qin, Liang
    Qin, Zheng-Hong
    Quaggin, Susan E
    Raben, Nina
    Rabinowich, Hannah
    Rabkin, Simon W
    Rahman, Irfan
    Rami, Abdelhaq
    Ramm, Georg
    Randall, Glenn
    Randow, Felix
    Rao, V Ashutosh
    Rathmell, Jeffrey C
    Ravikumar, Brinda
    Ray, Swapan K
    Reed, Bruce H
    Reed, John C
    Reggiori, Fulvio
    Régnier-Vigouroux, Anne
    Reichert, Andreas S
    Reiners, John J
    Reiter, Russel J
    Ren, Jun
    Revuelta, José L
    Rhodes, Christopher J
    Ritis, Konstantinos
    Rizzo, Elizete
    Robbins, Jeffrey
    Roberge, Michel
    Roca, Hernan
    Roccheri, Maria C
    Rocchi, Stephane
    Rodemann, H Peter
    Rodríguez de Córdoba, Santiago
    Rohrer, Bärbel
    Roninson, Igor B
    Rosen, Kirill
    Rost-Roszkowska, Magdalena M
    Rouis, Mustapha
    Rouschop, Kasper M A
    Rovetta, Francesca
    Rubin, Brian P
    Rubinsztein, David C
    Ruckdeschel, Klaus
    Rucker, Edmund B
    Rudich, Assaf
    Rudolf, Emil
    Ruiz-Opazo, Nelson
    Russo, Rossella
    Rusten, Tor Erik
    Ryan, Kevin M
    Ryter, Stefan W
    Sabatini, David M
    Sadoshima, Junichi
    Saha, Tapas
    Saitoh, Tatsuya
    Sakagami, Hiroshi
    Sakai, Yasuyoshi
    Salekdeh, Ghasem Hoseini
    Salomoni, Paolo
    Salvaterra, Paul M
    Salvesen, Guy
    Salvioli, Rosa
    Sanchez, Anthony M J
    Sánchez-Alcázar, José A
    Sánchez-Prieto, Ricardo
    Sandri, Marco
    Sankar, Uma
    Sansanwal, Poonam
    Santambrogio, Laura
    Saran, Shweta
    Sarkar, Sovan
    Sarwal, Minnie
    Sasakawa, Chihiro
    Sasnauskiene, Ausra
    Sass, Miklós
    Sato, Ken
    Sato, Miyuki
    Schapira, Anthony H V
    Scharl, Michael
    Schätzl, Hermann M
    Scheper, Wiep
    Schiaffino, Stefano
    Schneider, Claudio
    Schneider, Marion E
    Schneider-Stock, Regine
    Schoenlein, Patricia V
    Schorderet, Daniel F
    Schüller, Christoph
    Schwartz, Gary K
    Scorrano, Luca
    Sealy, Linda
    Seglen, Per O
    Segura-Aguilar, Juan
    Seiliez, Iban
    Seleverstov, Oleksandr
    Sell, Christian
    Seo, Jong Bok
    Separovic, Duska
    Setaluri, Vijayasaradhi
    Setoguchi, Takao
    Settembre, Carmine
    Shacka, John J
    Shanmugam, Mala
    Shapiro, Irving M
    Shaulian, Eitan
    Shaw, Reuben J
    Shelhamer, James H
    Shen, Han-Ming
    Shen, Wei-Chiang
    Sheng, Zu-Hang
    Shi, Yang
    Shibuya, Kenichi
    Shidoji, Yoshihiro
    Shieh, Jeng-Jer
    Shih, Chwen-Ming
    Shimada, Yohta
    Shimizu, Shigeomi
    Shintani, Takahiro
    Shirihai, Orian S
    Shore, Gordon C
    Sibirny, Andriy A
    Sidhu, Stan B
    Sikorska, Beata
    Silva-Zacarin, Elaine C M
    Simmons, Alison
    Simon, Anna Katharina
    Simon, Hans-Uwe
    Simone, Cristiano
    Simonsen, Anne
    Sinclair, David A
    Singh, Rajat
    Sinha, Debasish
    Sinicrope, Frank A
    Sirko, Agnieszka
    Siu, Parco M
    Sivridis, Efthimios
    Skop, Vojtech
    Skulachev, Vladimir P
    Slack, Ruth S
    Smaili, Soraya S
    Smith, Duncan R
    Soengas, Maria S
    Soldati, Thierry
    Song, Xueqin
    Sood, Anil K
    Soong, Tuck Wah
    Sotgia, Federica
    Spector, Stephen A
    Spies, Claudia D
    Springer, Wolfdieter
    Srinivasula, Srinivasa M
    Stefanis, Leonidas
    Steffan, Joan S
    Stendel, Ruediger
    Stenmark, Harald
    Stephanou, Anastasis
    Stern, Stephan T
    Sternberg, Cinthya
    Stork, Björn
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Subauste, Carlos S
    Sui, Xinbing
    Sulzer, David
    Sun, Jiaren
    Sun, Shi-Yong
    Sun, Zhi-Jun
    Sung, Joseph J Y
    Suzuki, Kuninori
    Suzuki, Toshihiko
    Swanson, Michele S
    Swanton, Charles
    Sweeney, Sean T
    Sy, Lai-King
    Szabadkai, Gyorgy
    Tabas, Ira
    Taegtmeyer, Heinrich
    Tafani, Marco
    Takács-Vellai, Krisztina
    Takano, Yoshitaka
    Takegawa, Kaoru
    Takemura, Genzou
    Takeshita, Fumihiko
    Talbot, Nicholas J
    Tan, Kevin S W
    Tanaka, Keiji
    Tanaka, Kozo
    Tang, Daolin
    Tang, Dingzhong
    Tanida, Isei
    Tannous, Bakhos A
    Tavernarakis, Nektarios
    Taylor, Graham S
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    Guidelines for the use and interpretation of assays for monitoring autophagy2012In: Autophagy, ISSN 1554-8627, Vol. 8, no 4, p. 445-544Article, review/survey (Refereed)
    Abstract [en]

    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

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    University of Tokyo, Japan .
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    Tokyo Metropolitan Institute Medical Science, Japan .
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    University of Texas MD Anderson Cancer Center.
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    Cincinnati Childrens Hospital Research Fdn, OH USA .
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    Eastern Michigan University.
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    National Cheng Kung University, Taiwan .
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    University of Michigan, MI USA .
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    National Institute Neurosci, Singapore .
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    Chang Gung University.
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    University of Medical and Dent New Jersey, NJ 08854 USA National Research Centre Environm and Heatlh, Germany .
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    University of Texas MD Anderson Cancer Centre, TX USA .
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    University of Oviedo, Spain .
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    Vanderbilt University, TN USA .
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    Istituto Superiore di Sanita.
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    Kyushu University, Japan .
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    GSF-National Research Center for Environment and Health.
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    University of Amsterdam, Netherlands .
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    CUNY, NY USA .
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    University of Padua, Italy .
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    University of Coll Antwerp, Belgium .
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    Tokyo Medical and Dent University, Japan .
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    INSERM, France IFR 50, France .
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    University of Utrecht, Netherlands .
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    Plymouth Marine Lab, England .
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    Centre Neurosci and Cell Biol, Portugal .
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    Saitama University, Japan .
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    Agriculture University of Warsaw, Poland .
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    NYU, NY USA .
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    Osaka University, Japan .
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    University of Tubingen, Germany .
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    University of Tokyo, Japan .
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    National Academic Science Ukraine, Ukraine .
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    University of Federal Sao Carlos, Brazil .
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    University of Bern, Switzerland .
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    Ist Ric Farmacol Mario Negri, Italy .
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    University of Oslo, Norway Norwegian Radium Hospital, Norway .
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    Case Western Reserve University, OH 44106 USA .
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    University of Leipzig, Germany .
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    Scripps Research Institute, FL USA .
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    Norwegian Radium Hospital, Norway .
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    National Hospital Org, Japan .
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    University of Ryukyus, Japan .
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    Yokohama City University, Japan .
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    Tokyo Metropolitan Institute Medical Science, Japan Tohoku University, Japan .
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    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
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    University of Insubria, Italy .
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    University of Penn, PA 19104 USA .
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    University of Gottingen, Germany .
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    Osaka University, Japan .
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    Juntendo University, Japan .
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    Central University of Venezuela, Venezuela .
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    University of Groningen, Netherlands .
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    Hospital Clin Barcelona, Spain .
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    Eotvos Lorand University, Hungary .
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    Abstract [en]

    Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

  • 29.
    Kurz, Tino
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Terman, Alexei
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric .
    Gustafsson, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Brunk, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Lysosomes and oxidative stress in aging and apoptosis2008In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1780, no 11, p. 1291-1303Article in journal (Refereed)
    Abstract [en]

    The lysosomal compartment consists of numerous acidic vesicles (pH ~ 4-5) that constantly fuse and divide. It receives a large number of hydrolases from the trans-Golgi network, while their substrates arrive from both the cell's outside (heterophagy) and inside (autophagy). Many macromolecules under degradation inside lysosomes contain iron that, when released in labile form, makes lysosomes sensitive to oxidative stress. The magnitude of generated lysosomal destabilization determines if reparative autophagy, apoptosis, or necrosis will follow. Apart from being an essential turnover process, autophagy is also a mechanism for cells to repair inflicted damage, and to survive temporary starvation. The inevitable diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow oxidative formation of lipofuscin in long-lived postmitotic cells, where it finally occupies a substantial part of the volume of the lysosomal compartment. This seems to result in a misdirection of lysosomal enzymes away from autophagosomes, resulting in depressed autophagy and the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. This scenario might put aging into the category of autophagy disorders. © 2008 Elsevier B.V. All rights reserved.

  • 30.
    Kurz, Tino
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Terman, Alexei
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Gustafsson, Bertil
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Brunk, Ulf T.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lysosomes In Iron Metabolism, Ageing And Apoptosis2008In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 129, no 4, p. 389-406Article in journal (Refereed)
    Abstract [en]

    The lysosomal compartment is essential for a variety of cellular functions, including the normal turnover of most long-lived proteins and all organelles. The compartment consists of numerous acidic vesicles (pH ~4-5) that constantly fuse and divide. It receives a large number of hydrolases (~50) from the trans-Golgi network, and substrates from both the cells’ outside (heterophagy) and inside (autophagy). Many macromolecules contain iron that gives rise to an iron-rich environment in lysosomes that recently have degraded such macromolecules. Iron-rich lysosomes are sensitive to oxidative stress, while ‘resting’ lysosomes, which have not recently participated in autophagic events, are not. The magnitude of oxidative stress determines the degree of lysosomal destabilization and, consequently, whether arrested growth, reparative autophagy, apoptosis, or necrosis will follow. Heterophagy is the first step in the process by which immunocompetent cells modify antigens and produce antibodies, while exocytosis of lysosomal enzymes may promote tumor invasion, angiogenesis, and metastasis. Apart from being an essential turnover process, autophagy is also a mechanism by which cells will be able to sustain temporary starvation and rid themselves of intracellular organisms that have invaded, although some pathogens have evolved mechanisms to prevent their destruction. Mutated lysosomal enzymes are the underlying cause of a number of lysosomal storage diseases involving the accumulation of materials that would be the substrate for the corresponding hydrolases, were they not defective. The normal, low-level diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow formation of lipofuscin in long-lived postmitotic cells, where it occupies a substantial part of the lysosomal compartment at the end of the life span. This seems to result in the diversion of newly produced lysosomal enzymes away from autophagosomes, leading to the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. If autophagy were a perfect turnover process, postmitotic ageing and several age-related neurodegenerative diseases would, perhaps, not take place.

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  • 31.
    Källdalen, Anette
    et al.
    Jönköping University, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Interests among older people in relation to gender, function and health-related quality of life2013In: British Journal of Occupational Therapy, ISSN 0308-0226, E-ISSN 1477-6006, Vol. 76, no 2, p. 87-93Article in journal (Refereed)
    Abstract [en]

    Abstract

    Introduction: Older people should have opportunities to be active participants in society as aspects such as lifestyle, physical and social environment and physical and mental status have influence on active ageing. The purpose was to explore the interests pursued by 85-year-old people living in ordinary housing in relation to gender, cognition, depression and health-related quality of life.

    Method: A sample of 240 participants completed a postal questionnaire including the EuroQoL health-related quality of life measurement. Additional instruments used during a subsequent home visit were the Canadian Occupational Performance Measure, Mini Mental State Examination and Geriatric Depression scale.

    Results: Women experienced poorer health than men, lived alone to a greater extent and used more mobility devices. Compared to men, women had a larger number of interests within household management, but no gender differences in the leisure area. Lower number of interests in active recreation was associated with lower cognitive function, poorer health-related quality of life and a higher risk of depressive symptoms.

    Conclusion: The main finding is that engaging in active recreation interests is associated with better cognition, less depression and higher health-related quality of life in these 85-year-old people and is therefore a concern of occupational therapists.

  • 32.
    Kågedal, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Scott Kim, Woojin
    Prince of Wales Medical Research Institute.
    Appelqvist, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
    Chan, Sharon
    Prince of Wales Medical Research Institute.
    Cheng, Danni
    Prince of Wales Medical Research Institute.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Geriatrics.
    Barnham, Kevin
    University of Melbourne.
    McCann, Heather
    Prince of Wales Medical Research Institute.
    Halliday, Glenda
    Prince of Wales Medical Research Institute.
    Garner, Brett
    Prince of Wales Medical Research Institute.
    Increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimers disease2010In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1801, no 8, p. 831-838Article in journal (Refereed)
    Abstract [en]

    The Niemann-Pick type Cl (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimers disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and we revealed that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals. In the cerebellum, a brain region that is relatively spared in AD, no difference in NPC1 expression was detected. Similarly, murine NPC1 mRNA levels were increased in the hippocampus of 12-month-old transgenic mice expressing a familial AD form of human amyloid-beta precursor protein (APP) and presenilin-1 (APP/PS1tg) compared to 12-month-old wild type mice, whereas no change in NPC1 was detected in mouse cerebellum. Immunohistochemical analysis of human hippocampus indicated that NPC1 expression was strongest in neurons. However, in vitro studies revealed that NPC1 expression was not induced by transfecting SK-N-SH neurons with human APP or by treating them with oligomeric amyloid-beta peptide. Total cholesterol levels were reduced in hippocampus from AD patients compared to control individuals, and it is therefore possible that the increased expression of NPC1 is linked to perturbed cholesterol homeostasis in AD.

  • 33.
    Landgren, Sara
    et al.
    University of Gothenburg, Sweden .
    von Otter, Malin
    University of Gothenburg, Sweden .
    Seibt Palmer, Mona
    University of Gothenburg, Sweden .
    Zetterstrom, Caroline
    University of Gothenburg, Sweden .
    Nilsson, Staffan
    Chalmers, Sweden .
    Skoog, Ingmar
    University of Gothenburg, Sweden .
    Gustafson, Deborah R.
    University of Gothenburg, Sweden .
    Minthon, Lennart
    Lund University, Sweden .
    Wallin, Anders
    University of Gothenburg, Sweden .
    Andreasen, Niels
    Karolinska Institute, Sweden .
    Bogdanovic, Nenad
    Karolinska Institute, Sweden .
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Blennow, Kaj
    University of Gothenburg, Sweden .
    Zetterberg, Henrik
    University of Gothenburg, Sweden UCL Institute Neurol, England .
    Kettunen, Petronella
    University of Gothenburg, Sweden .
    A novel ARC gene polymorphism is associated with reduced risk of Alzheimers disease2012In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 119, no 7, p. 833-842Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid beta (A beta) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute A beta application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and A beta(1-42). The AA genotype of the newly found 3-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.

  • 34.
    Lantz, Kristina
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Perceived participation and health-related quality of life in 85-year olds in Sweden2012In: OTJR (Thorofare, N.J.), ISSN 1539-4492, E-ISSN 1938-2383, Vol. 32, no 4, p. 117-125Article in journal (Refereed)
    Abstract [en]

    This study explores how 85-year-olds in Sweden perceive participation and autonomy in their life situations in relation to health-related quality of life and gender. A postal questionnaire included questions on socio-demographics, social network, assistive technology, community assistance, and the EQ-5D. During a home visit, an occupational therapist evaluated perceived participation and autonomy using the Impact on Participation and Autonomy Questionnaire. The majority perceived their participation as sufficient. Women had greater limitations than men in indoor and outdoor autonomy.  Only a few individuals reported many or severe problems with participation, mainly in mobility and leisure. Not having friends nearby, no close contact with neighbors, and living in community housing increased the risk of perceived problems. Sufficient participation was positively associated with higher HRQoL and facilitating participation is an area of interest for occupational therapists.

  • 35.
    Lorefält, Birgitta
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ganowiak, Wojchiec
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Pålhagen, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Unosson, Mitra
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Granerus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Factors of importance for weight loss in elderly patients with Parkinson's disease2004In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, no 3, p. 180-187Article in journal (Refereed)
    Abstract [en]

    Objective –  Weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon.

    Participants and methods –  Twenty-six l-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated.

    Results –  Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. Weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity.

    Conclusion –  Weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

  • 36.
    Lorefält, Birgitta
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Granerus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Weight Loss, Body Fat Mass, and Leptin in Parkinsons Disease2009In: MOVEMENT DISORDERS, ISSN 0885-3185, Vol. 24, no 6, p. 885-890Article in journal (Refereed)
    Abstract [en]

    Weight loss is a common problem in Parkinsons disease (PD), but the causative mechanisms behind this weight loss are unclear. We compared 2( PD patients with sex and age matched healthy controls. Examinations were repeated at baseline, after one and after two years. Body fat mass was measured by Dual X-ray Absorptiometry (DXA). Seventy three per cent of the PD patients lost body weight. Loss of body fat mass constituted a considerable part of the loss of body weight. In the patients who lost weight, serum leptin levels were lower than in those who did not lose weight. The relationship between low body fat mass and low leptin levels seems to be relevant, at least for female PD patients. It is reasonable to believe that low leptin levels in these patients could be secondary to the decreased body fat mass.

  • 37.
    Mattsson, N
    et al.
    University of Gothenburg.
    Rosen, E
    University of Gothenburg.
    Hansson, O
    Lund University.
    Andreasen, N
    Karolinska University Hospital.
    Parnetti, L
    University of Perugia.
    Jonsson, M
    University of Gothenburg.
    Herukka, S-K
    University of Eastern Finland.
    van der Flier, W M
    Vrije University of Amsterdam Medical Centre.
    Blankenstein, M A
    Vrije University of Amsterdam Medical Centre.
    Ewers, M
    University of Calif San Francisco.
    Rich, K
    NYU.
    Kaiser, E
    University of Heidelberg.
    Verbeek, M M
    Radboud University of Nijmegen Medical Centre.
    Olde Rikkert, M
    Radboud University of Nijmegen Medical Centre.
    Tsolaki, M
    Aristotle University of Thessaloniki.
    Mulugeta, E
    Kings College London.
    Aarsland, D
    Stavanger University Hospital.
    J Visser, P
    University of Maastricht.
    Schroeder, J
    University of Heidelberg.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    de Leon, M
    NYU.
    Hampel, H
    Goethe University of Frankfurt.
    Scheltens, P
    Vrije University of Amsterdam Medical Centre.
    Wallin, A
    University of Gothenburg.
    Eriksdotter-Jonhagen, M
    Karolinska University Hospital.
    Minthon, L
    Lund University.
    Winblad, B
    Karolinska University Hospital.
    Blennow, K
    University of Gothenburg.
    Zetterberg, H
    University of Gothenburg.
    Age and diagnostic performance of Alzheimer disease CSF biomarkers2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 78, no 7, p. 468-476Article in journal (Refereed)
    Abstract [en]

    Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. less thanbrgreater than less thanbrgreater thanMethods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. less thanbrgreater than less thanbrgreater thanResults: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. less thanbrgreater than less thanbrgreater thanConclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.

  • 38.
    Mattsson, Niklas
    et al.
    University of Gothenburg.
    Zetterberg, Henrik
    University of Gothenburg.
    Hansson, Oskar
    Lund University.
    Andreasen, Niels
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Parnetti, Lucilla
    University of Perugia, Italy.
    Jonsson, Michael
    University of Gothenburg.
    Herukka, Sanna-Kaisa
    University of Kuopio, Finland.
    van der Flier, Wiesje M.
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Blankenstein, Marinus A.
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Ewers, Michael
    University of Dublin, Ireland.
    Rich, Kenneth
    New York University, USA.
    Kaiser, Elmar
    University of Heidelberg, Germany.
    Verbeek, Marcel
    Radboud University Medical Centre, Nijmegen, the Netherlands.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Greece .
    Mulugeta, Ezra
    Stavanger University Hospital, Norway.
    Rosén, Erik
    University of Gothenburg.
    Aarsland, Dag
    Stavanger University Hospital, Norway.
    Jelle Visser, Pieter
    University of Maastricht, the Netherlands.
    Schroeder, Johannes
    University of Heidelberg, Germany.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    de Leon, Mony
    New York University, USA.
    Hampel, Harald
    University of Dublin, Ireland.
    Scheltens, Philip
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Pirttilae, Tuula
    University of Kuopio, Finland.
    Wallin, Anders
    University of Gothenburg.
    Eriksdotter Jönhagen, Maria
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Minthon, Lennart
    Lund University.
    Winblad, Bengt
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Blennow, Kaj
    University of Gothenburg.
    CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment2009In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 302, no 4, p. 385-393Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted.

    OBJECTIVE:

    To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI.

    DESIGN, SETTING, AND PARTICIPANTS:

    The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia.

    MAIN OUTCOME MEASURES:

    Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD.

    RESULTS:

    During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%.

    CONCLUSIONS:

    This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.

  • 39.
    Mjösberg, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Svensson, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Johansson, Emma
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hellström, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Boij, Roland
    Ryhov Hospital, Jönköping, Sweden.
    Matthiesen, Leif
    Helsingborg Hospital, Helsingborg, Sweden.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17θ-estradiol2009In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 183, no 1, p. 759-769Article in journal (Refereed)
    Abstract [en]

    CD4+CD25high regulatory T cells (Tregs) are implicated in the maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent, and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim of this study was to determine the frequency, phenotype, and function of circulating Tregs in the second trimester of human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expressions of Foxp3, CD127, and HLA-DR as determined by multicolor flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester of pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from nonpregnant women. By coculturing FACS-sorted Tregs and autologous CD4+CD25 responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as nonpregnant women in terms of suppressing IL-2, TNF-, and IFN- secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Furthermore, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need reevaluation.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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  • 40.
    Mårdh, Selina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Linnaeus Centre HEAD, Linköping University, Linköping, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Aspects of awareness in patients with Alzheimer's disease2013In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 25, no 7, p. 1167-1179Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of the present study was to gain insight into Alzheimer's disease (AD) patients' perception of the world through the study of a few aspects of awareness. The aspects in focus of the study were disease awareness, metacognition, managing of everyday life, and as a complement, the agreement (calibration) between patients and their spouses on the studied aspects was considered.

    Method: A mixed-method evaluation design was used involving 15 AD patients, their spouses, and 15 elderly healthy control subjects. The study comprised both a semistructured interview (AD patients and spouse) and a neuropsychological assessment (AD patients and control subjects).

    Results: The patients were aware of their disease and able to report on their illness. Despite this awareness, they were unable to realize and manage the practical and cognitive implications of their impairment. The results also indicate that patients and spouses were not well calibrated regarding thoughts about the disease and problems in handling the cognitive deterioration.

    Conclusions: The findings of our study have relevance to patients' well being and how they manage everyday life. An open dialogue on these issues between spouses and in the care for AD patients would hopefully enhance quality of life for all parties involved.

  • 41.
    Nath, Sangeeta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Roshan, Firoz
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Granseth, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid2012In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, no 26, p. 8767-8777Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of beta-amyloid (A beta) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble A beta oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric A beta. Additional studies conducted in a human donor-acceptor cell model show that this A beta transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular A beta oligomers play a role in neurodegeneration, and they explain the manner in which A beta can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.

  • 42.
    Navratil, M.
    et al.
    Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN, United States.
    Terman, Alexei
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric .
    Arriaga, E.A.
    Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN, United States.
    Giant mitochondria do not fuse and exchange their contents with normal mitochondria2008In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 314, no 1, p. 164-172Article in journal (Refereed)
    Abstract [en]

    Giant mitochondria accumulate within aged or diseased postmitotic cells as a consequence of insufficient autophagy, which is normally responsible for mitochondrial degradation. We report that giant mitochondria accumulating in cultured rat myoblasts due to inhibition of autophagy have low inner membrane potential and do not fuse with each other or with normal mitochondria. In addition to the low inner mitochondrial membrane potential in giant mitochondria, the quantity of the OPA1 mitochondrial fusion protein in these mitochondria was low, but the abundance of mitofusin-2 (Mfn2) remained unchanged. The combination of these factors may explain the lack of mitochondrial fusion in giant mitochondria and imply that the dysfunctional giant mitochondria cannot restore their function by fusing and exchanging their contents with fully functional mitochondria. These findings have important implications for understanding the mechanisms of accumulation of age-related mitochondrial damage in postmitotic cells. © 2007 Elsevier Inc. All rights reserved.

  • 43.
    Neselius, Sanna
    et al.
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Brisby, Helena
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Blennow, Kaj
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Zetterberg, Henrik
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    CSF-Biomarkers in Olympic Boxing: Diagnosis and Effects of Repetitive Head Trauma2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 4Article in journal (Refereed)
    Abstract [en]

    Background: Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur) boxing and cerebrospinal fluid (CSF) brain injury biomarkers. Methods: The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. Results: NFL (mean +/- SD, 5326 +/- 553 vs 135 +/- 51 ng/L p = 0.001), GFAP (496 +/- 238 vs 247 +/- 147 ng/L pless than0.001), T-tau (58 +/- 26 vs 49 +/- 21 ng/L pless than0.025) and S-100B (0.76 +/- 0.29 vs 0.60 +/- 0.23 ng/L p = 0.03) concentrations were significantly increased after boxing compared to controls. NFL (402 +/- 434 ng/L p = 0.004) and GFAP (369 +/- 113 ng/L p = 0.001) concentrations remained elevated after the rest period. Conclusion: Increased CSF levels of T-tau, NFL, GFAP, and S-100B in greater than80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury.

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  • 44.
    Neselius, Sanna
    et al.
    Sahlgrens University Hospital, Sweden .
    Zetterberg, Henrik
    Sahlgrens University Hospital, Sweden .
    Blennow, Kaj
    Sahlgrens University Hospital, Sweden .
    Randall, Jeffrey
    Quanterix Corp, MA USA .
    Wilson, David
    Quanterix Corp, MA USA .
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Brisby, Helena
    Sahlgrens University Hospital, Sweden .
    Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma2013In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 27, no 4, p. 425-433Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to investigate if olympic (amateur) boxing is associated with elevation of brain injury biomarkers in peripheral blood compared to controls. less thanbrgreater than less thanbrgreater thanMaterials and methods: Thirty olympic boxers competing in at least 47 bouts were compared to 25 controls. Blood was collected from the controls at one occasion and from the boxers within 1-6 days after a bout and after a rest period of at least 14 days. Tau concentration in plasma was determined using a novel single molecule ELISA assay and S-100B, glial fibrillary acidic protein, brain-derived neurotrophic factor and amyloid beta 1-42 were determined using standard immunoassays. less thanbrgreater than less thanbrgreater thanResults: None of the boxers had been knocked-out during the bout. Plasma-tau was significantly increased in the boxers after a bout compared to controls (mean +/- SD, 2.46 +/- 5.10 vs. 0.79 +/- 0.961 ngL(-1), p = 0.038). The other brain injury markers did not differ between the groups. Plasma-tau decreased significantly in the boxers after a resting period compared to after a bout (p = 0.030). less thanbrgreater than less thanbrgreater thanConclusions: Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.

  • 45.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Clinical and laboratory features and response to treatment in patients presenting with vitamin B-12 deficiency-related neurological syndromes - Invited comments: Neurol India. 2005 53(1):55-582005In: Neurology India, ISSN 0028-3886, E-ISSN 1998-4022, Vol. 53, no 1, p. 59-59p. 59-59Article in journal (Other academic)
    Abstract [en]

    Examines the clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Effects of vitamin B12 deficiency on enzymatic pathways; Cnversion of homocysteine to methionine and the conversion of methylmalonyl coenzyme A to succinyl coenzyme A; Methylation reactions involving homocysteine metabolism in the nervous system.

  • 46.
    Nägga, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Dong, Huan-Ji
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Olin Skoglund, Sabina
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health-related factors associated with hospitalization for old people: Comparisons of elderly aged 85 in a population cohort study2012In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 54, no 2, p. 391-397Article in journal (Refereed)
    Abstract [en]

    The aim of this population-based study was to (1) describe living conditions and actual health care utilization among 85 year olds; (2) determine factors that affect hospital admissions in this age. The study was conducted on 85-year-old residents in Linkoping municipality, Sweden. The data collected included medical records, health care utilization during the preceding 12 months and a postal questionnaire on assistance, assistive technology, functional impairment, feelings of loneliness, worries and health-related quality of life measured by the EQ-5D. Out of 650 eligible individuals, 496 (78% of those alive) participated. Despite the prevalence of multi-morbidity (68%) and mental discomfort, the majority managed self-care (85%), usual activities (74%) and had high (andgt;60/100) self-rated health evaluated by a visual analog scale (VAS). The non-hospitalized group reported a better health status than the hospitalized group in terms of medical aspects, living conditions and subjective estimation. Factors associated with in-patient care were an increased number of general practitioner visits, more assistive technology, community assistance, multimorbidity and/or diagnosed congestive heart failure and arrhythmia.

  • 47.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Gottfries, J.
    Medicinal Chemistry, AstraZeneca R and D, Mölndal, Sweden.
    Blennow, K.
    Department of Clinical Neuroscience, University of Göteborg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Cerebrospinal fluid phospho-tau, total tau and β-amyloid1-42 in the differentiation between Alzheimer's disease and vascular dementia2002In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 14, no 3-4, p. 183-190Article in journal (Refereed)
    Abstract [en]

    The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and β-amyloid1-42 (Aβ1-42). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer's disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Aβ1-42 was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Aβ1-42 in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.

  • 48.
    Nägga, Katarina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Effects of cobalamin supplementation - A study on dementia patients with cobalamin deficiency2002In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 23, no 1, p. 427-Conference paper (Other academic)
  • 49.
    Palhagen, S
    et al.
    Karolinska University.
    Granerus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Walinder, J
    University of Gothenburg.
    Svenningsson, P
    Karolinska University.
    Biomarker identification in CSF in patients with Parkinsons disease and major depression in EUROPEAN JOURNAL OF NEUROLOGY, vol 17, issue SI, pp 20-202010In: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2010, Vol. 17, no SI, p. 20-20Conference paper (Refereed)
    Abstract [en]

    n/a

  • 50.
    Palhagen, S.E.
    et al.
    Pålhagen, S.E., Department of Clinical Neuroscience, Division of Neurology Huddinge, Karolinska Institute, Stockholm, Sweden, Department of Neurology, Clinic of Medicine, Ryhov Hospital, Jönköping, Sweden, Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden, Department of Neurology, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
    Carlsson, M.
    Curman, E.
    Primary Care Centre, Eholmen, Linköping, Sweden.
    Walinder, J.
    Wålinder, J., Department of Psychiatry, Sahlgrenska University Hospital, Mölndal, Sweden.
    Granerus, Ann-Kathrine
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Depressive illness in Parkinson's disease - Indication of a more advanced and widespread neurodegenerative process?2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 117, no 5, p. 295-304Article in journal (Refereed)
    Abstract [en]

    Objective - The aims were to study if the type and complexity of Parkinsonian symptoms, as well as treatment, could be related to the occurrence and severity of later depressive symptoms. Furthermore, the aim was to study if there is a different depressive symptomatology in Parkinson's disease (PD) patients compared with depressive illness in an age-matched group of patients with major depression but without Parkinson's disease. Methods - Eleven PD-patients with major depression (MD) were compared to 14 PD-patients without depression and to 12 MD patients without PD. Results - PD patients who later developed a depressive illness were younger at the debut of PD than patients without depression (P < 0.05). At inclusion the depressed PD patients were more disabled than PD patients without depression with higher level in the H&Y scale (P<0.05), and they had more involuntary movements according to Unified Parkinson's Disease Rating Scale (UPDRS IV) (P < 0.01). A family history of depression was found in one third of the depressed non-parkinsonian patients but in none of the PD groups. Sleep disturbances were significantly more common among depressed PD patients than in PD patients without depression but even more common in depressed patients without PD. Conclusions - Depressed PD patients had a longer duration of PD and more severe motor symptoms than PD patients without depression, although tremor as an initial symptom seemed to be more common in PD without a later depression. It cannot be excluded that depression in PD reflects a more advanced and widespread neurodegeneration, including serotonergic as well as dopaminergic neurons. Sleep disturbances is common and could be overlooked as an expression of depression. © 2008 The Authors.

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