Aggregation of the Amyloid-β Peptide (Aβ40) within Condensates Generated through Liquid-Liquid Phase Separation

biorxiv(2023)

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Abstract
The deposition of the Aβ peptide into amyloid fibrils is characteristic of Alzheimer’s 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 Aβ could undergo liquid-liquid phase separation, and whether Aβ amyloid aggregation could take place within Aβ liquid condensates. By using a microfluidic protocol, we observed that the 40-residue form of Aβ (Aβ40) can undergo liquid-liquid phase separation, and that accessing a liquid intermediate state enhances primary nucleation and enables Aβ40 to readily self-assemble into amyloid fibrils. These results prompt further studies to investigate the possible role of Aβ condensates in the aggregation of this peptide in Alzheimer’s disease. ### Competing Interest Statement The authors have declared no competing interest.
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