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  • 1.
    Duits, Flora H.
    et al.
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    Teunissen, Charlotte E.
    Vrije University of Amsterdam, Netherlands.
    Bouwman, Femke H.
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    Visser, Pieter-Jelle
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands; University of Maastricht, Netherlands.
    Mattsson, Niklas
    Centre Imaging Neurodegenerat Disease, CA USA.
    Zetterberg, Henrik
    UCL Institute Neurol, England.
    Blennow, Kaj
    University of Gothenburg, Sweden.
    Hansson, Oskar
    Lund University, Sweden.
    Minthon, Lennart
    Lund University, Sweden.
    Andreasen, Niels
    Karolinska University Hospital, Sweden.
    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.
    Wallin, Anders
    University of Gothenburg, Sweden.
    Olde Rikkert, Marcel
    Donders Institute Brain Cognit and Behav, Netherlands.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Greece.
    Parnetti, Lucilla
    University of Perugia, Italy.
    Herukka, Sanna-Kaisa
    University of Eastern Finland, Finland; Kuopio University Hospital, Finland.
    Hampel, Harald
    University of Paris 06, France; University of Paris 06, France.
    De Leon, Mony J.
    NYU, NY USA.
    Schroeder, Johannes
    Heidelberg University, Germany.
    Aarsland, Dag
    Stavanger University Hospital, Norway.
    Blankenstein, Marinus A.
    Vrije University of Amsterdam, Netherlands.
    Scheltens, Philip
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    van der Flier, Wiesje M.
    Vrije University of Amsterdam, Netherlands.
    The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?2014In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 10, no 6, p. 713-723Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

  • 2.
    Lill, Christina M.
    et al.
    University of Lubeck, Germany; Max Planck Institute Molecular Genet, Germany.
    Rengmark, Aina
    Oslo University Hospital, Norway.
    Pihlstrom, Lasse
    Oslo University Hospital, Norway.
    Fogh, Isabella
    Kings Coll London, England.
    Shatunov, Aleksey
    Kings Coll London, England.
    Sleiman, Patrick M.
    Childrens Hospital Philadelphia, PA 19104 USA; Childrens Hospital Philadelphia, PA 19104 USA; University of Penn, PA 19104 USA; University of Turin, Italy.
    Wang, Li-San
    University of Penn, PA 19104 USA; University of Turin, Italy.
    Liu, Tian
    Max Planck Institute Human Dev, Germany.
    Lassen, Christina F.
    Danish Cancer Soc, Denmark.
    Meissner, Esther
    Max Planck Institute Molecular Genet, Germany.
    Alexopoulos, Panos
    Technical University of Munich, Germany.
    Calvo, Andrea
    University of Turin, Italy.
    Chio, Adriano
    University of Turin, Italy; Neurosci Institute Turin, Italy.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Faltraco, Frank
    Goethe University of Frankfurt, Germany.
    Forsgren, Lars
    Umeå University, Sweden.
    Kirchheiner, Julia
    University of Ulm, Germany.
    Kurz, Alexander
    Technical University of Munich, Germany.
    Larsen, Jan P.
    Stavanger University Hospital, Norway.
    Liebsch, Maria
    Max Planck Institute Molecular Genet, Germany.
    Linder, Jan
    Umeå University, Sweden.
    Morrison, Karen E.
    University of Birmingham, England; University Hospital Birmingham, England.
    Nissbrandt, Hans
    University of Gothenburg, Sweden.
    Otto, Markus
    University of Ulm, Germany.
    Pahnke, Jens
    University of Oslo, Norway; Oslo University Hospital, Norway; University of Lubeck, Germany.
    Partch, Amanda
    University of Penn, PA 19104 USA.
    Restagno, Gabriella
    Azienda Osped Citta Salute and Science, Italy.
    Rujescu, Dan
    University of Halle Wittenberg, Germany.
    Schnack, Cathrin
    University of Ulm, Germany.
    Shaw, Christopher E.
    Kings Coll London, England.
    Shaw, Pamela J.
    University of Sheffield, England.
    Tumani, Hayrettin
    University of Ulm, Germany.
    Tysnes, Ole-Bjorn
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Valladares, Otto
    University of Penn, PA 19104 USA.
    Silani, Vincenzo
    IRCCS Ist Auxol Italiano, Italy; University of Milan, Italy.
    van den Berg, Leonard H.
    University of Medical Centre Utrecht, Netherlands.
    van Rheenen, Wouter
    University of Medical Centre Utrecht, Netherlands.
    Veldink, Jan H.
    University of Medical Centre Utrecht, Netherlands.
    Lindenberger, Ulman
    Max Planck Institute Human Dev, Germany.
    Steinhagen-Thiessen, Elisabeth
    Charite, Germany.
    Teipel, Stefan
    German Centre Neurodegenerat Disease DZNE, Germany; University of Rostock, Germany.
    Perneczky, Robert
    Technical University of Munich, Germany; University of London Imperial Coll Science Technology and Med, England; West London Mental Health Trust, England.
    Hakonarson, Hakon
    Childrens Hospital Philadelphia, PA 19104 USA; Childrens Hospital Philadelphia, PA 19104 USA; University of Penn, PA 19104 USA.
    Hampel, Harald
    AXA Research Fund, France; University of Sorbonne, France.
    von Arnim, Christine A. F.
    University of Ulm, Germany.
    Olsen, Jorgen H.
    Danish Cancer Soc, Denmark.
    Van Deerlin, Vivianna M.
    University of Penn, PA 19104 USA; University of Turin, Italy.
    Al-Chalabi, Ammar
    Kings Coll London, England.
    Toft, Mathias
    Oslo University Hospital, Norway.
    Ritz, Beate
    ICM, France.
    Bertram, Lars
    Max Planck Institute Molecular Genet, Germany; University of Calif Los Angeles, CA USA.
    The role of TREM2 R47H as a risk factor for Alzheimers disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinsons disease2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 12, p. 1407-1416Article in journal (Refereed)
    Abstract [en]

    A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimers disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinsons disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2s role in AD may involve tau dysfunction. (C) 2015 The Alzheimers Association. Published by Elsevier Inc. All rights reserved.

  • 3.
    Mattsson, Niklas
    et al.
    Lund Univ, Sweden.
    Groot, Colin
    Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Jansen, Willemijn J.
    Maastricht Univ, Netherlands.
    Landau, Susan M.
    Univ Calif Berkeley, CA 94720 USA.
    Villemagne, Victor L.
    Austin Hlth, Australia; Austin Hlth, Australia.
    Engelborghs, Sebastiaan
    Univ Antwerp, Belgium.
    Mintun, Mark M.
    Avid Radiopharmaceut, PA USA.
    Lleo, Alberto
    Hosp Santa Creu and Sant Pau, Spain.
    Molinuevo, Jose Luis
    Clin Univ Hosp, Spain.
    Jagust, William J.
    Univ Calif Berkeley, CA 94720 USA.
    Frisoni, Giovanni B.
    Univ Hosp, Switzerland; Univ Hosp, Switzerland; Univ Geneva, Switzerland; IRCCS, Italy.
    Ivanoiu, Adrian
    Clin Univ Hosp, Spain; Catholic Univ Louvain, Belgium; Catholic Univ Louvain, Belgium.
    Chetelat, Gael
    Univ Caen Normandie, France.
    de Oliveira, Catarina Resende
    CHU Coimbra, Portugal.
    Rodrigue, Karen M.
    Univ Texas Dallas, TX USA.
    Kornhuber, Johannes
    Friedrich Alexander Univ Erlangen Nuremberg, Germany.
    Wallin, Anders
    Univ Gothenburg, Sweden.
    Klimkowicz-Mrowiec, Aleksandra
    Jagiellonian Univ, Poland.
    Kandimalla, Ramesh
    Postgrad Inst Med Educ and Res PGIMER, India.
    Popp, Julius
    Univ Hosp Lausanne, Switzerland.
    Aalten, Pauline P.
    Maastricht Univ, Netherlands.
    Aarsland, Dag
    Stavanger Univ Hosp, Norway.
    Alcolea, Daniel
    Hosp Santa Creu and Sant Pau, Spain.
    Almdahl, Ina S.
    Akershus Univ Hosp, Norway.
    Baldeiras, Ines
    CHU Coimbra, Portugal.
    van Buchem, Mark A.
    Leiden Univ, Netherlands.
    Cavedo, Enrica
    IRCCS, Italy; Univ Pierre and Marie Curie UPMC Paris 06, France.
    Chen, Kewei
    Banner Alzheimers Inst, AZ USA.
    Cohen, Ann D.
    Univ Pittsburgh, PA USA.
    Foerster, Stefan
    Tech Univ Munich, Germany.
    Fortea, Juan
    Hosp Santa Creu and Sant Pau, Spain.
    Frederiksen, Kristian S.
    Univ Copenhagen, Denmark.
    Freund-Levi, Yvonne
    Karolinska Univ, Sweden.
    Gill, Kiran Dip
    Postgrad Inst Med Educ and Res PGIMER, India.
    Gkatzima, Olymbia
    Aristotle Univ Thessaloniki, Greece.
    Grimmer, Timo
    Techn Univ Munchen, Germany.
    Hampel, Harald
    Univ Pierre and Marie Curie UPMC Paris 06, France; Ludwig Maximilians Univ Munchen, Germany; Ludwig Maximilians Univ Munchen, Germany.
    Herukka, Sanna-Kaisa
    Univ Eastern Finland, Finland; Kuopio Univ Hosp, Finland.
    Johannsen, Peter
    Rigshosp, Denmark.
    van Laere, Koen
    Katholieke Univ Leuven, Belgium.
    de Leon, Mony J.
    NYU, NY USA.
    Maier, Wolfgang
    Univ Bonn, Germany.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Meulenbroek, Olga
    Radboud Univ Nijmegen, Netherlands.
    Mollergard, Hanne M.
    Akershus Univ Hosp, Norway.
    Morris, John C.
    Washington Univ, MO 63110 USA.
    Mroczko, Barbara
    Med Univ Bialystok, Poland.
    Nordlund, Arto
    Univ Gothenburg, Sweden.
    Prabhakar, Sudesh
    Postgrad Inst Med Educ and Res PGIMER, India.
    Peters, Oliver
    German Ctr Neurodegenerat Dis DZNE, Germany.
    Rami, Lorena
    Clin Univ Hosp, Spain.
    Rodriguez-Rodriguez, Eloy
    Univ Hosp Marques Valdecilla, Spain.
    Roe, Catherine M.
    Washington Univ, MO 63110 USA.
    Ruther, Eckart
    Georg August Univ, Germany.
    Santana, Isabel
    CHU Coimbra, Portugal.
    Schroder, Johannes
    Heidelberg Univ, Germany.
    Seo, Sang W.
    Sungkyunkwan Univ, South Korea.
    Soininen, Hilkka
    Univ Eastern Finland, Finland; Kuopio Univ Hosp, Finland.
    Spiru, Luiza
    Carol Davila Univ Med and Pharm, Romania.
    Stomrud, Erik
    Lund Univ, Sweden.
    Struyfs, Hanne
    Univ Antwerp, Belgium.
    Teunissen, Charlotte E.
    Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Verhey, Frans R. J.
    Maastricht Univ, Netherlands.
    Vos, Stephanie J. B.
    Maastricht Univ, Netherlands.
    van Doorn, Linda J. C. van Waalwijk
    Radboud Univ Nijmegen, Netherlands; Radboud Univ Nijmegen, Netherlands.
    Waldemar, Gunhild
    Univ Copenhagen, Denmark.
    Wallin, Asa K.
    Lund Univ, Sweden.
    Wiltfang, Jens
    Georg August Univ, Germany; Georg August Univ, Germany.
    Vandenberghe, Rik
    Katholieke Univ Leuven, Belgium; Katholieke Univ Leuven, Belgium.
    Brooks, David J.
    Imperial Coll London, England.
    Fladby, Tormod
    Akershus Univ Hosp, Norway.
    Rowe, Christopher C.
    Austin Hlth, Australia; Austin Hlth, Australia.
    Drzezga, Alexander
    Univ Cologne, Germany.
    Verbeek, Marcel M.
    Radboud Univ Nijmegen, Netherlands; Radboud Univ Nijmegen, Netherlands.
    Sarazin, Marie
    Sorbonne Paris Cite, France.
    Wolk, David A.
    Univ Penn, PA 19104 USA.
    Fleisher, Adam S.
    Banner Alzheimers Inst, AZ USA; Eli Lilly, IN USA; Univ Calif San Diego, CA 92103 USA.
    Klunk, William E.
    Univ Pittsburgh, PA USA.
    Na, Duk L.
    Sungkyunkwan Univ, South Korea.
    Sanchez-Juan, Pascual
    Univ Hosp Marques Valdecilla, Spain.
    Lee, Dong Young
    Seoul Natl Univ, South Korea.
    Nordberg, Agneta
    Karolinska Univ Hosp, Sweden.
    Tsolaki, Magda
    Aristotle Univ Thessaloniki, Greece.
    Camus, Vincent
    Univ Francois Rabelais Tours, France.
    Rinne, Juha O.
    Univ Turku, Finland; Univ Turku, Finland; Turku Univ Hosp, Finland.
    Fagan, Anne M.
    Washington Univ, MO 63110 USA.
    Zetterberg, Henrik
    UCL, England; UK Dementia Res Inst, England; Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Rabinovici, Gil D.
    Univ Calif San Francisco, CA 94143 USA.
    Hansson, Oskar
    Lund Univ, Sweden.
    van Berckel, Bart N. M.
    Vrije Univ Amsterdam, Netherlands.
    van der Flier, Wiesje M.
    Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Scheltens, Philip
    Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Visser, Pieter Jelle
    Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands; Maastricht Univ, Netherlands.
    Ossenkoppele, Rik
    Lund Univ, Sweden; Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands; Vrije Univ Amsterdam, Netherlands.
    Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 913-924Article in journal (Refereed)
    Abstract [en]

    Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.

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