Competition between Fibrillation and Induction of Vesicle Fusion for the Membrane-Associated 40-Residue β-Amyloid Peptides

Abstract

Disruption of the cell membrane by the β-amyloid (Aβ) peptides has been considered as a main mechanism of Alzheimer's disease. The peptide-to-lipid molar ratio (P:L) varies over a broad range biologically. We report here that two of the previously observed Aβ evolution pathways, fibrillation and induction of vesicle fusion, compete with each other when P:L varies in model Aβ-liposome systems. Fibrillation is preferred at higher P:L values, and fusion is promoted at lower P:L values. Structural studies suggest that the same residues in Aβ may involve in both the initial fibrillation and membrane binding at the fusion sites.