Using an Amyloid Precursor Protein (APP) Reporter to Characterize α-Secretase

Human genetic studies suggest decreasing amyloid peptide (Aβ) levels in the brain could alter the course of Alzheimer's disease (AD) (1 -4). Proteolytic cleavages govern the level of Aβ generated from the amyloid precursor protein (APP). β- and γ-cleavages at the amino and carboxyl termini of Aβ produce amyloidogenic peptides; in contrast, α-cleavage within the Aβ domain destroys the amyloidogenic potential of APP. The proteases responsible for these cleavages have not been identified.