Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease

J Neurosci. 2008 Jun 18;28(25):6388-92. doi: 10.1523/JNEUROSCI.0364-08.2008.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive impairments in memory and cognition. Extracellular accumulation of soluble high-molecular-weight (HMW) Abeta oligomers has been proposed to be largely responsible for AD dementia and memory deficits in the Tg2576 mice, a model of AD. In this study, we found that a naturally derived grape seed polyphenolic extract can significantly inhibit amyloid beta-protein aggregation into high-molecular-weight oligomers in vitro. When orally administered to Tg2576 mice, this polyphenolic preparation significantly attenuates AD-type cognitive deterioration coincidentally with reduced HMW soluble oligomeric Abeta in the brain. Our study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat AD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal
  • Female
  • Flavonoids / isolation & purification
  • Flavonoids / therapeutic use*
  • Male
  • Mice
  • Mice, Transgenic
  • Phenols / isolation & purification
  • Phenols / therapeutic use*
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use
  • Polyphenols
  • Vitis*

Substances

  • Amyloid beta-Peptides
  • Flavonoids
  • Phenols
  • Plant Extracts
  • Polyphenols