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

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

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):
18562609
Funding Source:
National Center for Complementary and Alternative Medicine (NCCAM)
United States Department of Veterans Affairs (VA)
National Institute on Aging (NIA)
Alzheimer's Association
Life Science Research Foundation of Japan
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:
Natural Product
Therapeutic Agent:
Grape Seed Polyphenolic Extract (GSPE)
PubMed
ClinicalTrials
Patents
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Model Name:
Tg2576
ALZFORUM
Strain/Genetic Background:
Not Reported

Experimental Design

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

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Histopathology
beta Amyloid Deposits
beta Amyloid Load
Dense-core/Compact 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
Soluble Amyloid Precursor Protein alpha (sAPP alpha)
Soluble Amyloid Precursor Protein beta (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
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