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,,1
* Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA;
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA,
Geriatric Research and Clinical Center, James J. Peters VA Medical Center, Bronx, New York, USA; and
Food Science and Human Nutrition Department, University of Florida, Gainesville, Florida, USA
1Correspondence: Department of Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Pl., New York, NY 10029, USA. E-mail: giulio.pasinetti{at}mssm.edu
Recent studies suggest that moderate red wine consumption reduces the incidence of Alzheimer’s disease (AD) clinical dementia. Using Tg2576 mice, which model AD-type amyloid beta-protein (Aß) neuropathology, we tested whether moderate consumption of the red wine Cabernet Sauvignon modulates AD-type neuropathology and cognitive deterioration. The wine used in the study was generated using Cabernet Sauvignon grapes from Fresno, California, and was delivered to Tg2576 in a final concentration of 
6% ethanol. We found that Cabernet Sauvignon significantly attenuated AD-type deterioration of spatial memory function and Aß neuropathology in Tg2576 mice relative to control Tg2576 mice that were treated with either a comparable amount of ethanol or water alone. Chemical analysis showed the Cabernet Sauvignon used in this study contains a very low content of resveratrol (0.2 mg/L), 10-fold lower than the minimal effective concentration shown to promote Aß clearance in vitro. Our studies suggest Cabernet Sauvignon exerts a beneficial effect by promoting nonamyloidogenic processing of amyloid precursor protein, which ultimately prevents the generation of Aß peptides. This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia.—Wang, J., Ho, L., Zhao, Z., Seror, I., Humala, N., Dickstein, D. L., Meenakshisundaram, T., Percival, S. S., Talcott, S. T., Pasinetti, G. M. Moderate consumption of Cabernet Sauvignon attenuates Aß neuropathology in a mouse model of Alzheimer’s disease.
Key Words: APP • nonamyloidogenic • polyphenols • AD dementia
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