Bioavailability of grape‐derived polyphenolics and implications in Alzheimer's disease prevention and therapy

Abstract

The production and accumulation of β‐amyloid (Aβ) peptides is central to the pathogenesis of Alzheimer's disease (AD). Accumulating evidence suggests that selective bioactive grape‐derived polyphenols may protect against the AD‐type cognitive deterioration, in part, by interfering with Aβ‐mediated neuropathologic mechanisms. Results from our in vitro and in vivo studies suggest that select polyphenolics from red wines and Concord grape juice may inhibit the generation of Aβ peptides and/or the assembly of Aβ peptides into neurotoxic oligomeric Aβ aggregate species. We next explored the pharmacokinetic and bioavailability of red wine and grape juice polyphenolics to gather insights on the identity and bioactivity of specific polyphenolic components that might exert beneficial AD disease‐modifying activity in vivo. Specific polyphenolic derivatives that are bioavailable in the blood and/or in the brain have been identified. Ongoing studies are now exploring the potential role of these bioavailable polyphenolics in mitigating AD‐type neuropathologic and neurodegenerative mechanisms. Results from our studies provide further support for the inclusion of polyphenolics in the diet and the impetus to develop selective polyphenolic compounds for AD prevention and/or therapy.Supports: 1PO1AT004511‐01 Proj.‐1 (LH), 1PO1AT004511‐01 Proj.‐3 (GMP), J.J. Peters VA GRECC Program (GMP).