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The Journal of Neuroscience, June 18, 2008, 28(25):6388-6392; doi:10.1523/JNEUROSCI.0364-08.2008

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Brief Communications
Grape-Derived Polyphenolics Prevent Aβ Oligomerization and Attenuate Cognitive Deterioration in a Mouse Model of Alzheimer's Disease

Jun Wang,¹ Lap Ho,^1,4 Wei Zhao,¹ Kenjiro Ono,³ Clark Rosensweig,³ Linghong Chen,¹ Nelson Humala,¹ David B. Teplow,³ and Giulio M. Pasinetti^1,2,4

Departments of ¹Psychiatry and ²Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, ³Department of Neurology, David Geffen School of Medicine, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095, and ⁴Geriatric Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468

Correspondence should be addressed to Dr. Giulio M. Pasinetti, Icahn Research Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1230, New York, NY 10029. Email: giulio.pasinetti{at}mssm.edu

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive impairments in memory and cognition. Extracellular accumulation of soluble high-molecular-weight (HMW) Aβ oligomers has been proposed to be largely responsible for AD dementia and memory deficits in the Tg2576 mice, a model of AD. In this study, we found that a naturally derived grape seed polyphenolic extract can significantly inhibit amyloid β-protein aggregation into high-molecular-weight oligomers in vitro. When orally administered to Tg2576 mice, this polyphenolic preparation significantly attenuates AD-type cognitive deterioration coincidentally with reduced HMW soluble oligomeric Aβ in the brain. Our study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat AD.

Key words: Alzheimer's disease; Aβ peptide; amyloid β; cognitive; dementia; Morris water maze; spatial memory

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Received Sept. 27, 2007; revised May 3, 2008; accepted May 15, 2008.

Correspondence should be addressed to Dr. Giulio M. Pasinetti, Icahn Research Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1230, New York, NY 10029. Email: giulio.pasinetti{at}mssm.edu

This article has been cited by other articles:

				K. Ono, M. M. Condron, L. Ho, J. Wang, W. Zhao, G. M. Pasinetti, and D. B. Teplow Effects of Grape Seed-derived Polyphenols on Amyloid {beta}-Protein Self-assembly and Cytotoxicity J. Biol. Chem., November 21, 2008; 283(47): 32176 - 32187. [Abstract] [Full Text] [PDF]

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