The overall objective of this Center of Excellence for Research on Complementary and Alternative Medicine (CERC) in Alzheimer's disease application is to identify bioactive grape-derived polyhenols in AD prevention and/or therapy in the Tg2576 mouse model of Alzheimer's disease-type Ap neuropathology and cognitive deterioration. The overall research activities in this Center will explore grape-derived polyphenolic compounds for their potential roles of reduce Alzheimer's disease type cognitive deterioration in Tg2576 mice by reducing the accumulation of soluble extracellular oligomeric A|3 species in the brain. Based on this consideration, the purpose of Core C (Mouse Phenotyping Core) is to directly support the overall Center effort by facilitating the characterization of cognitive functions in Tg2576 mice in response to treatments with polyphenolic preparations from grape juice/wine (Project 1), the grape-derived polyphenolic, resveratrol (Project 2) and polyphenolic preparations from grape seed extract (Project 3). In recognition that multiple cognitive and behavioural modalities contribute to the overall cognitive functional status in higher animals, including human and AO mouse models, Core C will use multiple behavioural paradigms to provide a more comprehensive and sensitive measure of changes cognition function in response to polyphenolic treatments. Thus, the activity of Core C will integrate the specific goals of individual projects with the overall objective of this CERC in Alzheimer's disease application. The collective effort from the CERC in Alzheimer's disease will provide the rational basis for developing individual or a combination of grape-derived polyphenolic compounds for Alzheimer's disease prevention and/or therapy by modulating one or more of the AD-related mechanisms.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Program Projects (P01)
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Special Emphasis Panel (ZAT1-SM (07))
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Mount Sinai School of Medicine
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Ho, Lap; Ono, Kenjiro; Tsuji, Mayumi et al. (2018) Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms. Expert Rev Neurother 18:83-90
Chen, Tzu-Ying; Ferruzzi, Mario G; Wu, Qing-Li et al. (2017) Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat. Mol Nutr Food Res 61:
Varghese, Merina; Santa-Maria, Ismael; Ho, Lap et al. (2016) Extracellular Tau Paired Helical Filaments Differentially Affect Tau Pathogenic Mechanisms in Mitotic and Post-Mitotic Cells: Implications for Mechanisms of Tau Propagation in the Brain. J Alzheimers Dis 54:477-96
Blount, Jack W; Redan, Benjamin W; Ferruzzi, Mario G et al. (2015) Synthesis and quantitative analysis of plasma-targeted metabolites of catechin and epicatechin. J Agric Food Chem 63:2233-40
Hao, Ke; Di Narzo, Antonio Fabio; Ho, Lap et al. (2015) Shared genetic etiology underlying Alzheimer's disease and type 2 diabetes. Mol Aspects Med 43-44:66-76
Pasinetti, Giulio Maria; Wang, Jun; Ho, Lap et al. (2015) Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment. Biochim Biophys Acta 1852:1202-8
Hayden, Eric Y; Yamin, Ghiam; Beroukhim, Shiela et al. (2015) Inhibiting amyloid ?-protein assembly: Size-activity relationships among grape seed-derived polyphenols. J Neurochem 135:416-30
Villani, Tom S; Reichert, William; Ferruzzi, Mario G et al. (2015) Chemical investigation of commercial grape seed derived products to assess quality and detect adulteration. Food Chem 170:271-80
Wang, Dongjie; Ho, Lap; Faith, Jeremiah et al. (2015) Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease ?-amyloid oligomerization. Mol Nutr Food Res 59:1025-40
Ho, Lap; Ferruzzi, Mario G; Janle, Elsa M et al. (2013) Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. FASEB J 27:769-81

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