The abnormal deposition of the amyloid β-protein (Aβ) in the brain appears crucial to the pathogenesis of Alzheimer’s disease (AD). Recent studies have suggested that highly amyloidogenic Aβ1– 42 is a cause of neuronal damage leading to AD pathogenesis and that monomeric Aβ1– 40 has less neurotoxicity than Aβ1– 42. They found that mouse and human brain homogenates exhibit an enzyme activity converting Aβ1– 42 to Aβ1– 40 and that the major part of this converting activity is mediated by the angiotensin-converting enzyme (ACE). Purified human ACE converts Aβ1– 42 to Aβ1– 40 as well as decreases Aβ1– 42/Aβ1– 40 ratio and degrades Aβ1– 42 and Aβ1– 40. Importantly, the treatment of Tg2576 mice with an ACE inhibitor, captopril, promotes predominant Aβ1– 42 deposition in the brain, suggesting that ACE regulates Aβ1– 42/Aβ1– 40 ratio in vivo by converting secreted Aβ1– 42 to Aβ1– 40 and degrading Aβs. The upregulation of ACE activity can be a novel therapeutic strategy for AD.