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-beta (Abeta) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Abeta neuropathology and Abeta-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Abeta molecules to soluble high-molecular-weight Abeta 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 Abeta-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 Abeta-related mechanisms.