Aggregation of the amyloid-β peptide (Aβ40) within condensates generated through liquid-liquid phase separation.

ABSTRACT: The deposition of the amyloid-β (Aβ) peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Recently, it has been reported that some proteins can aggregate and form amyloids through an intermediate pathway involving a liquid-like condensed phase. These observations prompted us to investigate the phase space of Aβ. We thus explored the ability of Aβ to undergo liquid-liquid phase separation, and the subsequent liquid-to-solid transition that takes place within the resulting condensates. Through the use of microfluidic approaches, we observed that the 40-residue form of Αβ (Αβ40) can undergo liquid-liquid phase separation, and that accessing a liquid-like intermediate state enables Αβ40 to self-assemble and aggregate into amyloid fibrils through this pathway. These results prompt

SUBMITTER: Morris OM 

PROVIDER: S-EPMC11442885 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature