title: Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease.
abstract: 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, we 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. We 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. Our 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.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Pl., New York, NY 10029, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Ilana
authors.initials: I
authors.lastname: Seror
authors.forename: Nelson
authors.initials: N
authors.lastname: Humala
authors.forename: Dara L
authors.initials: DL
authors.lastname: Dickstein
authors.forename: Meenakshisundaram
authors.initials: M
authors.lastname: Thiyagarajan
authors.forename: Susan S
authors.initials: SS
authors.lastname: Percival
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Talcott
authors.forename: Giulio Maria
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000544:Alzheimer Disease / Q000473:pathology* / Q000517:prevention & control*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D010636:Phenols / Q000302:isolation & purification / Q000627:therapeutic use; D059808:Polyphenols; D011499:Protein Processing, Post-Translational; D014920:Wine / Q000032:analysis / Q000633:toxicity
chemical_list: D016564:Amyloid beta-Protein Precursor; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053829:Amyloid Precursor Protein Secretases