Alzheimer’s disease-linked Flemish APP mutation defines a distinct amyloid-β fold

Abstract

Cryogenic electron microscopy shows that the rare Flemish mutation in the amyloid-β precursor protein drives Aβ40 (an amyloid-β peptide) to assemble into a distinct filament fold. By exposing a phenylalanine residue, this fold creates a molecular feature that might explain the vascular accumulation of Aβ40 and associated cerebral hemorrhage in individuals carrying the Flemish mutation.