A Portrait of Alzheimer Secretases: New Features and Familiar Faces

The amyloid β-peptide (Aβ) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40- to 42-amino acid peptide is formed by the cleavage of the Aβ precursor protein (APP). The three proteases that cleave APP, α-, β-, and γ-secretases, have been implicated in the etiology of AD. β-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and α-secretase displays characteristics of certain membrane-tethered metalloproteases. γ-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the α-, β-, and γ-secretases provides potential targets for designing new drugs to treat AD.