liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Dissecting the Aggregation Events of Alzheimer’s disease Associated Aβ peptide Variants by the Combined use of Different Fluorescent Probes
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.ORCID iD: 0000-0002-5582-140X
Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The formation of soluble prefibrillar oligomeric species of the amyloid β peptide (Aβ) has been implicated as a causative agent in the development of Alzheimer’s disease (AD). It is therefore important to characterize the properties of these aggregates, which precede the formation of amyloid fibrils. We studied the in vitro aggregation process of two Aβ40 peptide variants through the combined use of four different fluorescent probes and transmission electron microscopy. Previous studies have shown that these two studied Aβ40 variants exhibit different levels of neurodegeneration when expressed in the central nervous system of Drosophila melanogaster. In the present study, we demonstrate distinct differences in aggregate morphology and their binding properties to different fluorescent probes during in vitro fibrillation of these Aβ peptides. Our results indicate a potential link between the observed neurodegenerative properties and the biophysical properties of distinct aggregated Aβ species.

National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-76739OAI: oai:DiVA.org:liu-76739DiVA: diva2:516567
Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2014-04-08
In thesis
1. The Alzheimer Aβ Peptide: Identification of Properties Distinctive for Toxic Prefibrillar Species
Open this publication in new window or tab >>The Alzheimer Aβ Peptide: Identification of Properties Distinctive for Toxic Prefibrillar Species
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Proteins must have specific conformations to function correctly inside cells. However, sometimes they adopt the wrong conformation, causing dysfunction and disease. A number of amyloid diseases are caused by misfolded proteins that form amyloid fibrils. One such disease is Alzheimer’s disease (AD). The protein involved in this deadly disease is the amyloid β (Aβ) peptide. The formation of soluble prefibrillar oligomeric Aβ species has been recognized as an important factor in the development of AD. The aim of work described in this thesis was to investigate which properties of these oligomeric species can be linked to toxicity. We approached this task by comparing the aggregation behavior and biophysical properties of aggregates formed by variants of the Aβ peptide that have been shown to differ in neurotoxicity when expressed in the central nervous system (CNS) of Drosophila melanogaster. A combined set involving different fluorescent probes was used in parallell with transmission electron microscopy. The toxicity of species formed during the aggregation process was examined by exposing human SH-SY5Y neuroblastoma cells to Aβ aggregates. We deduced that there is a correlation between cell toxicity and the propensity of the Aβ peptide to form small prefibrillar assemblies at an early stage of aggregation in vitro. Moreover, these prefibrillar species were characterized by their ability to be recognized by pentamer formyl thiophene acetic acid (p-FTAA) and the presence of exposed hydrophobic patches. We also found that larger aggregates did not induce cell death.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 44 p.
Series
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1526
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-76741 (URN)LIU-TEK-LIC-2012:11 (Local ID)978-91-7519-930-6 (ISBN)LIU-TEK-LIC-2012:11 (Archive number)LIU-TEK-LIC-2012:11 (OAI)
Presentation
2012-04-20, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (English)
Opponent
Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2012-12-04Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Göransson, Anna-LenaNilsson, PeterJohansson, Leif B. G.Nilsson, K. Peter RBrorsson, Ann-Christin

Search in DiVA

By author/editor
Göransson, Anna-LenaNilsson, PeterJohansson, Leif B. G.Nilsson, K. Peter RBrorsson, Ann-Christin
By organisation
Molecular BiotechnologyThe Institute of TechnologyOrganic ChemistryBiomolecular and Organic Electronics
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 92 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf