http://content.the-jci.org/articles/view/31547
Valsartan lowers brain beta-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, and
Giulio Maria Pasinetti

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 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. We
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.