The AβCs of Aβ-cleaving proteases

The amyloid β-protein (Aβ), which accumulates abnormally in Alzheimer disease (AD), is degraded by a diverse set of proteolytic enzymes. Aβ-cleaving proteases, largely ignored until only recently, are now known to play a pivotal role in the regulation of cerebral Aβ levels and amyloid plaque formation in animal models, and accumulating evidence suggests that defective Aβ proteolysis may be operative in many AD cases. This review summarizes the growing body of evidence supporting the involvement of specific Aβ-cleaving proteases in the etiology and potential treatment of AD. Recognition of the importance of Aβ degradation to the overall economy of Aβ has revised our thinking about the mechanistic basis of AD pathogenesis and identified a novel class of enzymes that may serve as both therapeutic targets and therapeutic agents.