Alzheimer's disease is a devastating disorder that strikes 1 in 10 Americans over age 65 and almost half of Americans over 85. The odds of developing Alzheimer's disease double every five years after age 65. While it is increasingly common to meet heart attack or cancer survivors, it is impossible to meet an Alzheimer's disease survivor because there are none. The Center of Excellence for Research on Complementary and Alternative Medicine (CERC) in Alzheimer's disease is a joint effort from investigators at Mount Sinai School of Medicine (MSSM), the Purdue University Botanical Research Center and collaborating institutions defines our vision for an integrated multidisciplinary program of preclinical research projects all linked by a unifying scientific theme related to the understanding of the potential protective roles of grape-derived polyphenols in Alzheimer's disease. There is mounting evidence that grape-derived polyphenols may beneficially influence Alzheimer's disease. However, because polyphenolic compositions and bioactivities vary considerably due to plant-growth environments, there are problems with the preparation of grape-derived polyphenols (and other dietary polyphenols). These limitations have prompted us to assemble groups of interdisciplinary scientists with expertise in Alzheimer's disease and nutritional-botanical sciences to design a series of studies with the ultimate goal of isolating and identifying, from dietary grape sources, bioactive and bioavailable polyphenolic compounds that are capable of providing beneficial Alzheimer's disease-modifying activities. Significant discoveries on the beneficial role of dietary polyphenolics in the prevention of Alzheimer's disease through the attenuation of (3-amyloid pathogenesis is providing new knowledge in novel pathogenic mechanisms and the possibility of novel potential solutions. The studies and the information that would be gleaned from this proposal are precisely on target to provide these insights. We are confident that the information that will come from this work will have a major impact on protective roles of grapederived polyphenols in Alzheimer's disease.

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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Hopp, Craig
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Icahn School of Medicine at Mount Sinai
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New York
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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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