Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment

Abstract

Alzheimer's disease (AD) is a devastating disorder that strikes 1 in 10 Americans over the age of 65, and almost half of all Americans over 85 years old. The odds of an individual developing AD double every five years after the age of 65. While it has become increasingly common to meet heart attack or cancer survivors, there are no AD survivors. There is mounting evidence that dietary polyphenols, including resveratrol, may beneficially influence AD. Based on this consideration, several studies reported in the last few years were designed to validate sensitive and reliable translational tools to mechanistically characterize brain bioavailable polyphenols as disease-modifying agents to help prevent the onset of AD dementia and other neurodegenerative disorders. Several research groups worldwide with expertise in AD, plant biology, nutritional sciences, and botanical sciences have reported very high quality studies that ultimately provided the necessary information showing that polyphenols and their metabolites, which come from several dietary sources, including grapes, cocoa etc., are capable of preventing AD. The ultimate goal of these studies was to provide novel strategies to prevent the disease even before the onset of clinical symptoms. The studies discussed in this review article provide support that the information gathered in the last few years of research will have a major impact on AD prevention by providing vital knowledge on the protective roles of polyphenols, including resveratrol. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

Keywords: Alzheimer's disease; Polyphenol; Resveratrol; SIRT1.

Figure 1

Brain-penetrating polyphenol metabolites derived from certain bioactive dietary polyphenol preparation may attenuate AD dementia by modulating Aβ and tau neuropathogenic mechanisms, neuroplasticity, and inflammatory mechanisms.

Figure 2. Bioactive Dietary Polyphenol Preparation (BDPP), a novel nutraceutical combination designed to simultaneously target multiple pathogenic mechanisms underlying AD

The schematic identifies the possible contribution of individual BDPP components for the prevention and therapeutic attenuation of AD dementia. Experimental evidence suggests that resveratrol may benefit AD dementia by promoting Aβ degradation and by decreasing neuroinflammation. We further proposed that application of resveratrol, along with other bioactive dietary polyphenol preparations, will modulate additional AD mechanisms (e.g., Aβ synthesis, Aβ aggregation, tau hyperphosphorylation, and tau aggregation), which will increase the likelihood of therapeutic success.