Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-type Neuropathology and Cognitive Deterioration

Article type: Research Article

Authors: Ho, Lap^{a; b; 1; *} | Chen, Ling Hong^{a; 1} | Wang, Jun^a | Zhao, Wei^a | Talcott, Stephen T.^c | Ono, Kenjiro^d | Teplow, David^d | Humala, Nelson^a | Cheng, Alice^a | Percival, Susan S.^e | Ferruzzi, Mario^f | Janle, Elsa^f | Dickstein, Dara L.^g | Pasinetti, Giulio Maria^{a; b; g}

Affiliations: [a] Department of Psychiatry, Mount Sinai School of Medicine, NY, USA | [b] Geriatric Research and Clinical Center, James J. Peters VA Medical Center, Bronx, NY, USA | [c] Department of Nutrition and Food Science, Texas A&M University, College Stations, TX, USA | [d] Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [e] Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, USA | [f] Foods and Nutrition Department, Purdue University, West Lafayette, IN, USA | [g] Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA

Correspondence: [*] Corresponding author: Lap Ho, Ph.D., Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10019, USA. Tel.: +1 718 584 9000 x1829; E-mail: [email protected].

Note: [1] Both authors contributed equally to this work.

Abstract: We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-β (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms.

Keywords: Alzheimer's disease dementia, amyloid-β protein precursor (AβPP), high-molecular-weight amyloid-β oligomer species, polyphenols

DOI: 10.3233/JAD-2009-0916

Journal: Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 59-72, 2009