Pyroglutamate-modified Aβ(3-42) affects aggregation kinetics of Aβ(1-42) by accelerating primary and secondary pathways.

ABSTRACT: The aggregation into amyloid fibrils of amyloid-β (Aβ) peptides is a hallmark of Alzheimer's disease. A variety of Aβ peptides have been discovered in vivo, with pyroglutamate-modified Aβ (pEAβ) forming a significant proportion. pEAβ is mainly localized in the core of plaques, suggesting a possible role in inducing and facilitating Aβ oligomerization and accumulation. Despite this potential importance, the aggregation mechanism of pEAβ and its influence on the aggregation kinetics of other Aβ variants have not yet been elucidated. Here we show that pEAβ(3-42) forms fibrils much faster than Aβ(1-42) and the critical concentration above which aggregation was observed was drastically decreased by one order of magnitude compared to Aβ(1-42). We elucidated the co-aggregation mechanism of

SUBMITTER: Dammers C 

PROVIDER: S-EPMC5612032 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature