Red wine, resveratrol, and Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. No effective therapies for AD are yet available, and potentially preventive lifestyle factors, including diet and physical activity, have become a focus of AD research. One such factor is moderate wine consumption, which has been claimed to be neuroprotective, and some studies have suggested a potential role for grapes and wine in retarding cognitive decline and other effects of aging. Polyphenols contained in grapes have been investigated as a preventive measure or potential therapy for dementia. The best-studied fruit polyphenol, the stilbenoid resveratrol (trans-3,5,4’-trihydroxystilbene), is known for its anti-oxidant and anti-inflammatory properties. The present short review evaluates the evidence regarding the role of red wine and resveratrol in the prevention and treatment of AD. Some research findings have suggested that resveratrol may be useful in the treatment of neurodegenerative diseases, including AD, due to its ability to reduce cognitive decline and to inhibit amyloid β aggregation in animal models of dementia. Studies in rodents have demonstrated neuroprotective effects of resveratrol on central features of AD, including decreased amyloid deposition and tau-hyperphosphorylation, enhanced hippocampal neurogenesis, and improved memory functions. The mechanisms through which resveratrol exerts neuroprotective efficacy in animals remain to be established. The potential of resveratrol to act as a nutraceutical targeting neuropathological changes in AD and exerting neuroprotective efficacy may be related to its anti-oxidant activities and its ability to antagonize amyloid aggregation, suppress neuroinflammation, decrease mitochondrial dysfunction, and modulate signaling pathways. In contrast to the neuroprotective activity of resveratrol in various in-vitro and in-vivo models, evidence of the ability of resveratrol to prevent age-associated neurodegeneration in humans and to improve cognitive deficits in AD is lacking. Thus, whether resveratrol has any beneficial effects in humans remains to be established. Pterostilbene (trans-3,5-dimethoxy-4’-hydroxystilbene), an analog of resveratrol, appears to be more effective than resveratrol in ameliorating brain alterations associated with aging and may be a more promising compound for future research. Moderate red wine intake is unable to provide resveratrol in amounts required for clinically relevant effects in AD. Were resveratrol proven to be effective in combatting AD, supplements or a drug should be substituted for wine as a source. Moreover, the toxic effects of alcohol should be considered, since recent evidence suggests that no level of alcohol consumption has beneficial health effects. In particular, long-term alcohol consumption, even in moderate quantities, is associated with multiple markers of abnormal brain structure, including hippocampal atrophy. Moderate drinking to promote brain health is not justified, and any claims regarding the potential efficacy of red wine in the prevention of AD are unsubstantiated and irresponsible.