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Apolipoprotein E impairs amyloid-β fibril elongation and maturation
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2019 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658Article in journal (Refereed) Epub ahead of print
Abstract [en]

Alzheimer's disease (AD) is strongly linked to amyloid depositions of the Aβ peptide (Aβ). The lipid-binding protein apolipoprotein E (ApoE) has been found to interfere with Aβ amyloid formation and to exert a strong clinical impact to the pathology of AD. The APOE gene exists in three allelic isoforms represented by APOE ε2, APOE ε3, and APOE ε4. Carriers of the APOE ε4 variant display a gene dose-dependent increased risk of developing the disease. Aβ amyloids are formed via a nucleation-dependent mechanism where free monomers are added onto a nucleus in a template-dependent manner. Using a combination of surface plasmon resonance and thioflavin-T assays, we here show that ApoE can target the process of fibril elongation and that its interference effectively prevents amyloid maturation. We expose a complex equilibrium where the concentration of ApoE, Aβ monomers, and the amount of already formed Aβ fibrils will affect the relative proportion and formation rate of mature amyloids versus alternative assemblies. The result illustrates a mechanism which may affect both the clearance rate of Aβ assemblies in vivo and the population of cytotoxic Aβ assemblies.

Place, publisher, year, edition, pages
2019.
Keywords [en]
abeta, amyloid, apolipoprotein E, elongation, surface plasmon resonance
National Category
Basic Medicine Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
biological chemistry
Identifiers
URN: urn:nbn:se:umu:diva-165305DOI: 10.1111/febs.15075PubMedID: 31571352OAI: oai:DiVA.org:umu-165305DiVA, id: diva2:1371511
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2019-11-20

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Islam, TohidulGharibyan, Anna L.Brännström, KristofferHedberg, IsabellOlofsson, Anders

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Islam, TohidulGharibyan, Anna L.Brännström, KristofferHedberg, IsabellOlofsson, Anders
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The FEBS Journal
Basic MedicineMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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