Hexameric β-amyloid as a key assembly in Alzheimer's disease : cellular formation and seeding effects
(2021)
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- Authors
- Supervisors
- Kienlen-Campard, Pascal
- Abstract
- The β-amyloid peptide (Aβ) is the major constituent of senile plaques, a characteristic lesion of Alzheimer's disease (AD). Aβ is released by the metabolism of a precursor protein through the action of the γ-secretase complex, whose catalytic activity is ensured by either presenilin 1 (PS1) or 2 (PS2). Following their release as monomers, Aβ peptides are prone to aggregate. Under pathological conditions, this leads to the formation of Aβ fibrils which deposit in senile plaques. However, it is now recognized that the intermediate forms of Aβ, called oligomers, correlate better with AD pathology. In this work, we characterize a specific cell-derived oligomeric form, hexameric Aβ, as a readily formed Aβ assembly that can serve as a nucleus to enhance the aggregation process. More precisely, we identify hexameric Aβ as both a novel biomarker for AD and a potential therapeutic target. Specifically, we propose a direct link between PS2-dependent γ-secretase activity and the cellular release of hexameric Aβ, potentially responsible for its spread.
- Affiliations
Citations
Vrancx, C. (2021). Hexameric β-amyloid as a key assembly in Alzheimer’s disease : cellular formation and seeding effects. https://hdl.handle.net/2078.5/115202