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


Year of Publication:
Contact PI Name:
Dennis J. Selkoe
Contact PI Affiliation:
Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Matthew L. Hemming, Wesley Farris
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

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 β-protein (Aβ), a putative upstream initiator of Alzheimer disease. These studies support the hypothesis that deficiency in ACE-mediated Aβ proteolysis could increase Alzheimer disease risk, and raise the question of whether ACE inhibitors, a commonly prescribed class of anti-hypertensive medications, can elevate Aβ levels in vivo. To test this hypothesis, this study tested the administration of the ACE inhibitor captopril to two lines of APP transgenic mice harboring either low levels of Aβ or high levels of Aβ with associated plaque deposition. In both models, they show that captopril does not affect cerebral Aβ levels in either soluble or insoluble pools. Further, they found no change in plaque deposition or in peripheral Aβ levels. Data from these Alzheimer models suggest that captopril and similar ACE inhibitors do not cause Aβ accumulation in vivo.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Angiotensin I Converting Enzyme (ACE)
Therapeutic Notes:
Angiotensin I converting enzyme has been nominated as a potential target for AD. Nominated targets are obtained from several sources, including the National Institute on Aging's Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) consortium. Targets have been identified using computational analyses of high-dimensional genomic, proteomic and/or metabolomic data derived from human samples. See Agora link for more information.

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:
Not Reported
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
beta Amyloid Load
Angiotensin Converting Enzyme (ACE)
Brain-beta Amyloid Peptide-Total
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Organs-beta Amyloid Peptides
Brain-Detergent Soluble beta Amyloid Peptide 40
Brain-Detergent Soluble beta Amyloid Peptide 42
Brain-beta Amyloid Deposits
Target Engagement (Inhibition Angiotensin Converting Enzyme )