Beneficial effects of white wine polyphenols-enriched diet on Alzheimer's disease-like pathology

The development of effective medicines to break or delay the progressive brain degeneration underlying cognitive decline and dementia that characterize Alzheimer's disease (AD) is one of the greatest challenges of our time. In the present work, a selective pool of polyphenols, obtained from the white wine by adsorption to polyvinylpyrrolidone polymer (PVPP), was used to prepare a polyphenols-enriched diet, supplementing the drinking water with 100 mg/L (expressed as gallic acid equivalent) of wine polyphenolic extract. The impact of the daily consumption of water supplemented with polyphenols for 2 months on brain of 10-month-old 3xTg-AD and NonTg mice was evaluated, considering effects on the redox state of cells, levels of amyloid-β peptides, mitochondrial bioenergetics and fatty acid profile of whole membrane phospholipids. The polyphenols-enriched diet promotes brain accumulation of catechin and hydroxybenzoic acid derivatives, and modulates the redox state of 3xTg-AD brain cells, increasing both glutathione/glutathione disulfide ratio and catalase activity and decreasing membrane lipids oxidation. Additionally, the functional diet decreases the 3xTg-AD brain levels of both amyloid-β peptides, Aβ1-40 and Aβ1-42. However, the brain mitochondrial bioenergetic dysfunction of 3xTg-AD animals was not attenuated by the polyphenols-enriched diet. Lipidomic studies showed that this functional diet modulates membrane lipid composition of brain cells, increasing C22:6n-3 (docosahexanoic acid) and decreasing C20:4n-6 (arachidonic acid) levels, which may have beneficial impact on the chronic inflammatory process associated with AD pathology. Altogether, these results indicate that the oral administration of this polyphenols-enriched diet promotes significant benefits in multiple aspects of the pathophysiological cascade associated with the neuropathology developed by 3xTg-AD mice.