Aggregation of the Amyloid-beta Peptide (Abeta40) within Condensates Generated through Liquid-Liquid Phase Separation

The deposition of the A{beta} peptide into amyloid fibrils is characteristic of Alzheimers disease. As it has been recently observed that the process of amyloid aggregation can take place within an intermediate liquid-like condensed phase, we investigated whether A{beta} could undergo liquid-liquid phase separation, and whether A{beta} amyloid aggregation could take place within A{beta} liquid condensates. By using a microfluidic protocol, we observed that the 40-residue form of A{beta} (A{beta}40) can undergo liquid-liquid phase separation, and that accessing a liquid intermediate state enhances primary nucleation and enables A{beta}40 to readily self-assemble into amyloid fibrils. These results prompt further studies to investigate the possible role of A{beta} condensates in the aggregation of this peptide in Alzheimers disease.