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

Jun Wang, Lap Ho, Linghong Chen, Zhong Zhao, Wei Zhao, Xianjuan Qian, Nelson Humala, Ilana Seror, Sadie Bartholomew, Clive Rosendorff, Giulio Maria Pasinetti

Research output: Contribution to journalArticlepeer-review

284 Scopus citations


Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We 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 β-amyloid protein (Aβ) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Aβ peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Aβ peptides in the brain. Most importantly, valsartan administration also attenuated the development of Aβ-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 Aβ-related memory deficits in subjects with AD or in those at high risk of developing AD.

Original languageEnglish
Pages (from-to)3393-3402
Number of pages10
JournalJournal of Clinical Investigation
Issue number11
StatePublished - 1 Nov 2007


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