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Apolipoprotein E impairs amyloid‐β fibril elongation and maturation
Author(s) -
Islam Tohidul,
Gharibyan Anna L.,
Golchin Solmaz A.,
Pettersson Nina,
Brännström Kristoffer,
Hedberg Isabell,
Virta MeritMiriam,
Olofsson Linnea,
Olofsson Anders
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15075
Subject(s) - apolipoprotein e , fibril , thioflavin , amyloid (mycology) , chemistry , biophysics , monomer , biochemistry , microbiology and biotechnology , biology , alzheimer's disease , medicine , disease , polymer , inorganic chemistry , organic chemistry
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.