Lifelong Management of Amyloid-Beta Metabolism to Prevent Alzheimer's Disease

Twenty-five years ago, the cloning and localization to chromosome 21 of the Alzheimer's amyloid-beta (Aβ) precursor protein (APP)1 made clear that the early-onset form of Alzheimer's disease that occurs in all patients with Down's syndrome2 is apparently attributable to an extra copy of APP. Proamyloidogenic APP missense mutations were subsequently identified in families with autosomal dominant Alzheimer's disease,3 and a substantial proportion of cases of autosomal dominant Alzheimer's disease have been linked to more than 200 proamyloidogenic mutations in the catalytic subunits of γ-secretase (known as presenilin 14 and 25) that are responsible for the liberation of Aβ . . .