Angiotensin-converting Enzyme Degrades Alzheimer Amyloid β-Peptide (Aβ); Retards Aβ Aggregation, Deposition, Fibril Formation; and Inhibits Cytotoxicity

Abstract

We have demonstrated that the angiotensin-converting enzyme (ACE) genotype is associated with Alzheimer's disease (AD) in the Japanese population (1). To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid -peptide (A) in vitro. Surprisingly, ACE was found to significantly inhibit A aggregation in a dose response manner. The inhibition of aggregation was specifically blocked by preincubation of ACE with an ACE inhibitor, lisinopril. ACE was confirmed to retard A fibril formation with electron microscopy. ACE inhibited A deposits on a synthaloid plate, which was used to monitor A deposition on autopsied brain tissue.