Characterization of brain bioactive polyphenols as disease modifying agents in Alzheimer's disease

Alzheimer's disease (AD) is a devastating disorder that strikes 1 in 10 Americans over the age of 65 and almost half of Americans over 85 years old. The odds of developing AD double every five years after age 65. There is mounting evidence that dietary polyphenols may beneficially influence AD. The Center of Excellence for Research on Complementary and Alternative Medicine (CERC) in Alzheimer's disease defines our vision for an integrated multidisciplinary program of preclinical research projects all linked by the unifying scientific theme of understanding the potential protective roles of grape-derived polyphenols in AD. In 2008, a marketing report suggested that more than eight percent of nutraceutical consumers indicated that they had purchased food products aiming to prevent an undesirable condition, and fifty percent of consumers reported purchasing foods to manage or treat conditions. Much of this consumer demand for therapeutic food products is for foods containing polyphenols. However, because polyphenolic compositions and bioactivities vary considerably due to plant-growth environments, there are problems with the preparation of grape-derived polyphenolics (and other dietary polyphenolics). For the same reason, there are also issues that complicate the harvest, storage and processing/preparation of certain dietary sources of polyphenols. These limitations prompted us to assemble groups of interdisciplinary scientists with expertise in Alzheimer's disease and nutritional-botanical sciences to design a series of studies with the ultimate goal of isolating and identifying bioactive polyphenolic compounds from dietary grape sources that are capable of providing beneficial Alzheimer's disease-modifying activities. The studies conducted in our Center employ mechanistic-based approaches to validate sensitive and reliable translational tools to detect and assess relevant signatures of brain bioavailable polyphenols as disease modifying agents in Alzheimer's disease by measuring efficacy as well as other outcomes mechanistically. The anticipated goals of our Center have thus far been met by successfully identifying select dietary grape polyphenol compounds capable of attenuating AD-type cognitive dementia in models of AD-type β-amyloid pathogenesis. We recently succeeded in the isolation and structural identification of brain bioavailable, bioactive polyphenol metabolites from dietary grape products. Our studies have also provided for the first time the much need information for an ongoing translational Phase II clinical study exploring the feasibility of developing a select polyphenol preparation for the treatment of AD.