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

The deposition of the amyloid-beta (A beta) 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 A beta. We thus explored the ability of A beta 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 Alpha beta (Alpha beta 40) can undergo liquid-liquid phase separation, and that accessing a liquid-like intermediate state enables Alpha beta 40 to self-assemble and aggregate into amyloid fibrils through this pathway. These results prompt further studies to investigate the possible role of Alpha beta liquid-liquid phase separation and its subsequent aggregation in the context of Alzheimer's disease and more generally on neurodegenerative processes.