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

Bibliographic

Year of Publication: 
2008
Contact PI Name: 
Giulio Maria Pasinetti
Contact PI Affiliation: 
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA
Co-Authors: 
Jun Wang, Lap Ho, Wei Zhao, Kenjiro Ono, Clark Rosensweig, Linghong Chen, Nelson Humala, David B. Teplow
Primary Reference (PubMED ID): 
Funding Source:
Study Goal and Principal Findings: 

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, was 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. This study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat AD.

Therapeutic Agent

Therapeutic Information: 
Therapy Type:

Animal Model

Model Information: 
Species:
Model Type:
Strain/Genetic Background: 
Not Reported

Experimental Design

Is the following information reported in the study?: 
Power/Sample Size Calculation
Blinded for Treatment
Pharmacokinetic Measures
Toxicology Measures
Biomarkers
Formulation
Duration of Treatment
Age of Animal at the Beginning of Treatment
Sex as a Biological Variable
Number of Premature Deaths
Statistical Plan
Inclusion/Exclusion Criteria Included
Randomized into Groups
Blinded for Outcome Measures
Pharmacodynamic Measures
ADME Measures
Dose
Route of Delivery
Frequency of Administration
Age of Animal at the End of Treatment
Study Balanced for Sex as a Biological Variable
Number of Excluded Animals
Genetic Background
Conflict of Interest

Outcomes

Outcomes: 
Outcome MeasuredOutcome Parameters
Behavioral
  • Morris Water Maze
  • Histopathology
  • beta amyloid deposits
  • beta amyloid load
  • Dense-core Plaques
  • Biochemical
  • Brain-buffer soluble beta amyloid peptide 40
  • Brain-buffer soluble beta amyloid peptide 42
  • alpha Secretase Activity
  • beta Secretase Activity
  • gamma Secretase Activity
  • sAPP alpha
  • sAPP beta
  • Brain-beta amyloid oligomers
  • Amyloid Precursor Protein (APP)
  • Neprilysin
  • Insulin Degrading Enzyme (IDE)
  • Biomarker
  • Serum-beta amyloid peptides
  • Toxicology
  • Body Weight
  • Water Consumption
  • Liver Enzymes