Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid β-protein metabolism in mouse models of Alzheimer disease

Genetic and pathologic studies have associated angiotensin-converting enzyme (ACE) with Alzheimer disease. Previously, we and others have reported that ACE degrades in vitro the amyloid beta-protein (A beta), a putative upstream initiator of Alzheimer disease. These studies support the hypothesis that deficiency in ACE-mediated A beta proteolysis could increase Alzheimer disease risk and raise the question of whether ACE inhibitors, a commonly prescribed class of anti-hypertensive medications, can elevate A beta levels in vivo. To test this hypothesis, we administered the ACE inhibitor captopril to two lines of APP transgenic mice harboring either low levels of A beta or high levels of A beta with associated plaque deposition. In both models, we show that captopril does not affect cerebral A beta levels in either soluble or insoluble pools. Furthermore, we find no change in plaque deposition or in peripheral A beta levels. Data from these Alzheimer models suggest that captopril and similar ACE inhibitors do not cause A beta accumulation in vivo. (c) 2007 Elsevier Inc. All rights reserved.