The p3 peptides (Aβ_17-40/42) rapidly form amyloid fibrils that cross-seed with full-length Aβ.

ABSTRACT: The p3 peptides, Aβ_17-40/42, are a common alternative cleavage product of the amyloid precursor protein, and are found in diffuse amyloid deposits of Alzheimer's and Down Syndrome brains. The p3 peptides have been mis-named 'non-amyloidogenic'. Here we show p3_40/42 peptides rapidly form amyloid fibrils, with kinetics dominated by secondary nucleation. Importantly, cross-seeding experiments, with full-length Aβ induces a strong nucleation between p3 and Aβ peptides. The cross-seeding interaction is highly specific, and occurs only when the C-terminal residues are matched. We have imaged membrane interactions with p3, and monitored Ca²⁺ influx and cell viability with p3 peptide. Together this data suggests the N-terminal residues influence, but are not essent

SUBMITTER: Tian Y 

PROVIDER: S-EPMC11868391 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature