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Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease

Bibliographic

Year of Publication:
2006
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, Zhong Zhao, Ilana Seror, Nelson Humala, Dara L. Dickstein, Meenakshisundaram Thiyagarajan, Susan S. Percival, Stephen T. Talcott
Primary Reference (PubMED ID):
Funding Source:
Altschul Foundation
James J. Peters VA Geriatrics Research Education and Clinical Center Program
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Recent studies suggest that moderate red wine consumption reduces the incidence of Alzheimer's disease (AD) clinical dementia. Using Tg2576 mice, which model AD-type amyloid beta-protein (Abeta) neuropathology, was tested whether moderate consumption of the red wine Cabernet Sauvignon modulates AD-type neuropathology and cognitive deterioration. The wine used in the study was generated using Cabernet Sauvignon grapes from Fresno, California, and was delivered to Tg2576 in a final concentration of approximately 6% ethanol. Was found that Cabernet Sauvignon significantly attenuated AD-type deterioration of spatial memory function and Abeta neuropathology in Tg2576 mice relative to control Tg2576 mice that were treated with either a comparable amount of ethanol or water alone. Chemical analysis showed the Cabernet Sauvignon used in this study contains a very low content of resveratrol (0.2 mg/L), 10-fold lower than the minimal effective concentration shown to promote Abeta clearance in vitro. This studies suggest Cabernet Sauvignon exerts a beneficial effect by promoting nonamyloidogenic processing of amyloid precursor protein, which ultimately prevents the generation of Abeta peptides. This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Cabernet Sauvignon
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
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
Barnes Maze
Histopathology
Dense-core/Compact Plaques
Activated Astrocytes
Biochemical
Glial Fibrillary Acidic Protein (GFAP)
APP-CTF83 (CTF alpha)
APP-CTF99 (CTF beta)
Brain-Guanidine Soluble beta Amyloid Peptide 40
Brain-Guanidine Soluble beta Amyloid Peptide 42
gamma Secretase Activity
alpha Secretase Activity
beta Secretase Activity
Amyloid Precursor Protein (APP)
APP-CTFs
Soluble Amyloid Precursor Protein alpha (sAPP alpha)
Soluble Amyloid Precursor Protein beta (sAPP beta)
Pharmacokinetics
Drug Concentration-Serum
Toxicology
Food Intake
Water Consumption
Body Weight
Bilirubin
Alanine Aminotransferase (ALT)
Aspartate Aminotransferase (AST)