Alzheimer's disease prevention by flavonols and their analogs.

Four studies now document reduced incidence of Alzheimer's disease (AD) or dementia diagnoses in aging individuals who report higher dietary intake of flavonols (or their glycosides) years prior to diagnosis vs those with lower intake. These effects are large, almost 50 %, for individuals at higher genetic risk for AD, providing a robust gene x environment interaction. They display a specific structure-activity relationship. These benefits are driven by modest-to-moderate differences in the quantity of flavonol (glycoside) consumed. These data contrast with the failure of late life supplementation with flavonol-rich ginko extract to alter progression to AD in groups of individuals who are not selected for genotype or dietary pattern. Studies of mouse AD models support benefits of the flavonol quercetin. In vitro and in vivo results add the receptor type protein tyrosine phosphatase PTPRD to the list of oxidative and other targets or mechanisms to which flavonol benefits are attributed. The magnitude of flavonol protection for individuals who would otherwise be especially vulnerable to AD, the ease of supplementation strategies with currently-available nutraceuticals and the opportunities for development of improved flavonol analogs all support further exploration of flavonol-based strategies for reducing the incidence of AD with aging.