10-26-2007
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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 ß-amyloid protein (Aß) accumulation.
Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Aß 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 Aß peptides in the brain.
Most importantly, valsartan administration also attenuated the development of Aß-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 Aß-related memory deficits in subjects with AD or in those at high risk of developing AD.
Source: The Journal of Clinical Investigation, October 25, 2007. DOI:10.1172/JCI31547. By Wang J, Ho L, Chen L, Zhao Z, Zhao W, Qian X, Humala N, Seror I, Batholomew S, Rosendorff C, Pasinetti GM. Departments of Psychiatry, Neuroscience, Medicine, Mount Sinai School of Medicine, New York; Geriatric Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, New York, New York, USA. [ E-mail: giulio.pasinetti@mssm.edu ]
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