Rare Flemish Alzheimer's mutation uncovers a novel amyloid fold fueling vascular brain damage

A rare Flemish APP mutation in Alzheimer's alters the folding of amyloid-beta into a previously unseen Z-shaped filament that tends to accumulate around brain vessels, driving cerebral amyloid angiopathy and hemorrhage. Using cryo-EM, researchers show how loss of a methyl group at residue 21 promotes this vascular-prone fold, offering new targets for therapies and broader insight into Alzheimer’s pathology across its variants.