β-Amyloid Degradation and Alzheimer's Disease

Abstract

Extensiveβ-amyloid (Aβ) deposits in brain parenchyma in the form of senile plaques and in blood vessels in the form of amyloid angiopathy are pathological hallmarks of Alzheimer's disease (AD). The mechanisms underlying Aβdeposition remain unclear. Major efforts have focused on Aβproduction, but there is little to suggest that increased production of Aβplays a role in Aβdeposition, except for rare familial forms of AD. Thus, other mechanisms must be involved in the accumulation of Aβin AD. Recent data shows that impaired clearance may play an important role in Aβaccumulation in the pathogenesis of AD. This review focuses on our current knowledge of Aβ-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), insulin-degrading enzyme (IDE), angiotensin-converting enzyme (ACE), and the plasmin/uPA/tPA system as they relate to amyloid deposition in AD.