The overall objective of this Center of Excellence for Research on Complementary and Alternative Medicine 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 proposed studies in this application are based on our hypothesize that selective bioactive grape-derived polyphenols protects against the onset and progression of AD-type cognitive deterioration by inhibiting the generation of A/7peptides from the amyloid precursor protein. We will test this hypothesis by using bio-guided fractionation methodologies to generate polyphenol preparations with progressively less complexity from Cabernet Sauvignon and from Concord purple grape juice that will exert A0- lowering activity in the Tg2576 AD mouse model. We will continue to explore the efficacy of ApMowering polyphenol preparations to attenuate the onset and progression of AD-type cognitive deterioration in Tg2576 mice and to clarify the mechanisms of action. The proposed studies in this application will complement the other Research Projects in this Center application and elucidate general mechanisms by which grape-derived polyphenolics may blunt age-related Alzheimer's disease, especially in a growing population affected by mild cognitive impairment that is at high risk for AD. Outcomes of the proposed studies will likely result in the development of selective grape-derived polyphenolic compounds as lead compounds for clinical testing in Alzheimer's disease

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Program Projects (P01)
Project #
1P01AT004511-01
Application #
7394216
Study Section
Special Emphasis Panel (ZAT1-SM (07))
Project Start
2007-09-01
Project End
2012-08-31
Budget Start
2007-09-30
Budget End
2008-09-29
Support Year
1
Fiscal Year
2007
Total Cost
$77,949
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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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