Mutations of all genes known to be involved in familial AD - presenilin-1 (PSEN1), PSEN2, and amyloid precursor protein (APP) - contribute to increased absolute or relative production of the 42-amino-acid-length cleavage product of APP, beta-amyloid (Aβ), which is the main constituent of the amyloid plaques that characterize AD [4]. This evidence concerns the gene PSEN1 and Alzheimer disease.