Polyphenols are a large and diverse group of naturally occurring compounds widely distributed in many plant-derived foods and beverages. Polyphenols are receiving increasing attention for their roles in preventing the onset and progression of Alzheimer’s disease (AD). In particular, preclinical evidence demonstrated the efficacy of certain polyphenols, acting individually or in combination, to modulate multiple diverse mechanisms relevant to AD, implicating the potential for novel development of polyphenols for multi-target engagement in AD. Despite the increasing efforts committed to clinical testing of polyphenols in AD, these are hindered by limited knowledge of polyphenol bioavailability, specific forms of brain-bioavailable bioactive polyphenols (including polyphenol metabolites) and their underlying mechanisms of actions. I will discuss the mechanistic implications of brain-bioavailable bioactive polyphenol metabolites in modulating key physiological processes that are relevant in early, preclinical AD. I will also summarize current efforts for the characterization of brain-bioavailable bioactive polyphenols and their potential drug-like properties for their successful clinical development into nutraceuticals. Moreover, promoting cognitive resilience and preventing cognitive deterioration in response to external stressors is one of the most difficult challenges in the promotion of healthy brain aging and the prevention of AD. Emerging evidence suggests that the promotion of resilience against psychological stress and other mood disorders by select microbiome derived polyphenol metabolites may be tightly associated with the onset and progression of AD. Based on this consideration, I will also discuss novel evidence on the role of the gastrointestinal microbiome, specifically the contributions of microbiota in modulating bioconversion and bioavailability of bioactive phenolic acids from the polyphenols. Collectively, I will critically discuss the current complex mosaic of evidence, which puts the investigation of brain-bioavailable bioactive polyphenols at the cross-roads between promotion of psychological resilience and prevention of AD cognitive deterioration, and eventually the translation of select brain-bioavailable bioactive polyphenols into therapeutic nutraceuticals.

Role of polyphenols in promotion of healthy brain aging and Alzheimer’s disease preventative initiatives

251st National Meeting (2016)

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