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Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease


Year of Publication:
Contact PI Name:
Giulio Maria Pasinetti
Contact PI Affiliation:
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA
Jun Wang, Lap Ho, Linghong Chen, Zhong Zhao, Wei Zhao, Xianjuan Qian, Nelson Humala, Ilana Seror, Sadie Bartholomew, Clive Rosendorff
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
James J. Peters VA Geriatrics Research Education and Clinical Center Program
Altschul Foundation
Study Goal and Principal Findings:

Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). Was screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type beta-amyloid protein (Abeta) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Abeta peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. Was found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Abeta peptides in the brain. Most importantly, valsartan administration also attenuated the development of Abeta-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Abeta-related memory deficits in subjects with AD or in those at high risk of developing AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Angiotensin II Receptor Type 1

Animal Model

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

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
Morris Water Maze
beta Amyloid Deposits
beta Amyloid Load
Dense-core/Compact Plaques
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
alpha Secretase Activity
gamma Secretase Activity
beta Secretase Activity
APP-CTF83 (CTF alpha)
APP-CTF99 (CTF beta)
Insulin Degrading Enzyme (IDE)
Amyloid Precursor Protein (APP)
Insulin Degrading Enzyme (IDE) Activity
Endothelin Converting Enzyme 1 (ECE1)
beta Amyloid Aggregation
Brain-beta Amyloid Oligomers
Blood Pressure
Serum-beta Amyloid Peptides
Cell Biology
beta Amyloid Peptides
Body Weight
Water Consumption
Glucose Tolerance Test