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DOI: 10.1055/s-0032-1315377
Novel Role of Red Wine-Derived Polyphenols in the Prevention of Alzheimerʼs Disease Dementia and Brain Pathology: Experimental Approaches and Clinical Implications
Publication History
received 03 May 2012
revised 13 July 2012
accepted 22 August 2012
Publication Date:
21 September 2012 (online)
![](https://www.thieme-connect.de/media/plantamedica/201215/lookinside/thumbnails/10.1055-s-0032-1315377-1.jpg)
Abstract
Recent studies suggest that by the middle of this century, as many as 14 million Americans will have Alzheimerʼs disease, creating an enormous strain on families, the health care system and the federal budget. There are still widespread misconceptions about issues related to the prevention and/or treatment of disease pathogenesis, leaving us unprepared to deal with the disease. To address these challenges, several therapeutic approaches are currently under investigation, mainly in an attempt to delay disease onset and eventually slow down its progression. Recent epidemiological evidence has implicated the protective role of dietary polyphenols from grape products against Alzheimerʼs disease. Furthermore, experimental evidence supports the hypothesis that certain bioactive grape-derived polyphenols may protect against Alzheimerʼs disease-type cognitive deterioration, in part by interfering with the generation and assembly of β-amyloid peptides into neurotoxic oligomeric aggregated species. Brain-targeting polyphenols have been shown to significantly reduce the generation of β-amyloid peptides in primary cortico-hippocampal neuron cultures, and preliminary results indicate that they may influence neuronal synaptic plasticity. Recent evidence has also implicated the role of certain grape-derived preparations in beneficially modulating tau neuropathology, including reducing tau aggregation. Studies suggest that dietary polyphenolics may benefit Alzheimerʼs disease by modulating multiple disease-modifying modalities, both β-amyloid-dependent and independent mechanisms, and provide impetus for the development of polyphenolic compounds for Alzheimerʼs disease prevention and/or therapy.
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References
- 1 Alzheimerʼs Association. 2008 Alzheimerʼs disease facts and figures. Alzheimerʼs & Dementia 2008; 4: 110-133
- 2 Cummings JL. Treatment of Alzheimerʼs disease: current and future therapeutic approaches. Rev Neurol Dis 2004; 1: 60-69
- 3 Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimerʼs disease. Acta Neuropathol 2009; 118: 5-36
- 4 Davies P, Koppel J. Mechanism-based treatment for Alzheimerʼs disease. Dialogues Clin Neurosci 2009; 11: 159-169
- 5 Bertram L, Tanzi RE. Thirty years of Alzheimerʼs disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008; 9: 768-778
- 6 Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimerʼs disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimerʼs disease. Nat Med 1996; 2: 864-870
- 7 Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon MN, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S. Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1. Nature 1996; 383: 710-713
- 8 Cleary JP, Wash DM, Hofmeister JJ, Shankar M, Kuskowski MA, Selkoe DJ, Ashe KH. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 2005; 8: 79-84
- 9 Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Boxlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, Bloom FE. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimerʼs disease. Proc Natl Acad Sci USA 2006; 103: 5161-5166
- 10 Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ. Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticithy in vivo . Nat Med 2005; 11: 556-561
- 11 Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2005; 440: 352-357
- 12 Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo . Nature 2002; 416: 535-539
- 13 Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimerʼs disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356
- 14 Goedert M. Tau protein and the neurofibrillary pathology of Alzheimerʼs disease. Ann NY Acad Sci 1996; 77: 121-131
- 15 Sahara N, Maeda S, Takashima A. Tau oligomerization: a role for tau aggregation intermediates linked to neurodegeneration. Curr Alzheimer Res 2008; 5: 591-598
- 16 Berger Z, Roder H, Hanna A, Carlson A, Rangachari V, Yue M, Wszolek Z, Ashe K, Knight J, Dickson D, Andorfer C, Rosenberry TL, Lewis J, Hutton M, Janus C. Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci 2007; 27: 3650-3652
- 17 Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, Deture M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005; 309: 476-481
- 18 Sorrentino G, Bonavita V. Neurodegeneration and Alzheimerʼs disease: the lesson from tauopathies. Neurol Sci 2007; 28: 63-71
- 19 Ramesh BN, Rao TS, Prakasam A, Sambamurti K, Rao KS. Neuronutrition and Alzheimerʼs disease. J Alzheimers Dis 2010; 19: 1123-1139
- 20 Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G. Correlative memory deficits. Aβ elevation, and amyloid plaques in transgenic mice. Science 1996; 274: 99-102
- 21 Brouillard R, George F, Fougerousse A. Polyphenols produced during red wine ageing. Biofactors 1997; 6: 403-410
- 22 Cantos E, Espin JC, Tomas-Barberan FA. Varietal differences among the polyphenol profiles of seven table grape cultivars studied by LC-DAD-MS-MS. J Agric Food Chem 2002; 50: 5691-5696
- 23 De La Hera Orts ML, Martinez-Cutillas A, Lopez Roca JM, Perez-Prieto E, Gomez-Plaze E. Effect of deficit irrigation on anthocyanin content of Monastrell grapes and wines. J Int Sci Vigne Vin 2005; 39: 47-55
- 24 Lee JE, Hwang GS, Van Den BF, Lee CH, Hong YS. Evidence of vintage effects on grape wines using 1H NMR-based metabolomic study. Anal Chim Acta 2009; 648: 71-76
- 25 Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79: 727-747
- 26 Pérez-Jiménez J, Neveu V, Vos F, Scalbert A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr 2010; 64 (Suppl. 03) S112-S120
- 27 Radovanovic BC, Radovanovic AN, Souquet JM. Phenolic profile and free radical-scavenging activity of Cabernet Sauvignon wines of different geographical origins from the Balkan region. J Sci Food Agric 2010; 90: 2455-2461
- 28 Yokotsuka K, Nagao A, Nakazawa K, Sato M. Changes in anthocyanins in berry skins of Merlot and Cabernet Sauvignon grapes grown in two soils modified with limestone or oyster shell versus a native soil over two years. AmJ Enol Viticult 1999; 50: 1-12
- 29 Xu Y, Simon JE, Welch C, Wightman JD, Ferruzzi MG, Ho L, Passinetti GM, Wu Q. Survey of polyphenol constituents in grapes and grape-derived products. J Agric Food Chem 2011; 59: 10586-10593
- 30 Barnes S, Prasain J, DʼAlessandro T, Arabshahi A, Botting N, Lila MA, Jackson G, Janle EM, Weaver CM. The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food Funct 2011; 2: 235-244
- 31 Wu Z, Ming J, Gao R, Wang Y, Liang Q, Yu H, Zhao G. Characterization and antioxidant activity of the complex of tea polyphenols and oat β-glucan. J Agric Food Chem 2011; 59: 10737-10746
- 32 Semalty A, Semalty M, Rawat MS, Franceschi F. Supramolecular phospholipids-polyphenolics interactions: the PHYTOSOME strategy to improve the bioavailability of phytochemicals. Fitoterapia 2010; 81: 306-314
- 33 Monagas M, Urpi-Sarda M, Sánchez-Patán F, Llorach R, Garrido I, Gómez-Cordovés C, Andres-Lacueva C, Bartolomé B. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct 2010; 1: 233-253
- 34 Ferruzzi MG, Lobo JK, Janle EM, Cooper B, Simon JE, Wu QL, Welch C, Ho L, Weaver C, Pasinetti GM. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimerʼs disease. J Alzheimers Dis 2009; 18: 113-124
- 35 Yang CS, Sang S, Lambert JD, Lee MJ. Bioavailability issues in studying the health effects of plant polyphenolic compounds. Mol Nutr Food Res 2008; 52 (Suppl. 01) S139-S151
- 36 Galli F. Interactions of polyphenolic compounds with drug disposition and metabolism. Curr Drug Metab 2007; 8: 830-838
- 37 Silberberg M, Besson C, Manach C, Remesy C, Morand C. Influence of dietary antioxidants on polyphenol intestinal absorption and metabolism in rats. J Agric Food Chem 2006; 54: 3541-3546
- 38 Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS. Piperine enhances the bioavailability of the tea polyphenol (−)-epigallocatechin-3-gallate in mice. J Nutr 2004; 134: 1948-1952
- 39 Forester SC, Waterhouse AL. Metabolites are key to understanding health effects of wine polyphenolics. J Nutr 2009; 139: 1824S-1831S
- 40 Wang J, Ferruzzi MG, Ho L, Blount J, Janle EM, Gong B, Pan Y, Gowda GA, Raftery D, Arrieta-Cruz I, Sharma V, Cooper B, Lobo J, Simon JE, Zhang C, Cheng A, Qian X, Ono K, Teplow DB, Pavlides C, Dixon RA, Pasinetti GM. Brain-targeted proanthocyanidin metabolites for Alzheimerʼs disease treatment. J Neurosci 2012; 32: 5144-5150
- 41 Wang J, Ho L, Zhao W, Ono K, Rosensweig C, Chen L, Humala N, Teplow DB, Pasinetti GM. Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimerʼs disease. J Neurosci 2008; 28: 6388-6392
- 42 Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST, Pasinetti GM. Moderate consumption of Cabernet Sauvignon attenuated beta-amyloid neuropathology in a mouse model of Alzheimer/s disease. FASEB J 2006; 20: 2313-2320
- 43 Ho L, Chen LH, Wang J, Zhao W, Talcott ST, Ono K, Teplow D, Humala N, Cheng A, Percival SS, Ferruzzi M, Janle E, Dickstein DL, Pasinetti GM. Heterogeneity in red wine polyphenolic contents differentially influences Alzheimerʼs disease-type neuropathology and cognitive deterioration. J Alzheimers Dis 2009; 16: 59-72
- 44 Bitan G, Lomakin A, Teplow DB. Amyloid beta-protein oligomerization: prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins. J Biol Chem 2001; 276: 35176-35184
- 45 Pasinetti GM, Wang J, Marambaud P, Ferruzzi M, Gregor P, Knable LA, Ho L. Neuroprotective and metabolic effects of resveratrol: therapeutic implications for Huntingtonʼs disease and other neurodegenerative disorders. Exp Neurol 2011; 232: 1-6
- 46 Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimerʼs disease amyloid-β peptides. J Biol Chem 2005; 280: 37377-37382
- 47 Ho L, Pasinetti GM. Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding. Expert Rev Proteomics 2010; 7: 579-589
- 48 Wang J, Santa-Maria I, Ho L, Ksiezak-Reding H, Ono K, Teplow DB, Pasinetti GM. Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimerʼs disease. J Alzheimers Dis 2010; 22: 653-661
- 49 Santa-Maria I, Diaz-Ruiza C, Ksiezak-Reding H, Chen A, Ho L, Wang J, Pasinetti GM. GSPE interferes with tau aggregation in vivo: implication for treating tauopathy. Neurobiol Aging 2012; 33: 2072-2081