Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer's disease via modulation of proteolytic mechanisms

Cumulative evidence indicates that excessive consumption of calories from saturated fat contributes to the development Alzheimer's disease (AD). Here, we assess triggering and progression AD pathology induced by a high-fat diet (HFD), effects resveratrol, polyphenol found in common dietary sources with pleiotropic neuroprotective activities. Over 16 weeks, male wild type (WT) transgenic 5XFAD mice were fed control diet, HFD (60% kcal fat), or supplemented 0.1% resveratrol. Resveratrol protected against HFD-induced memory loss WT prevented mice. also reduced amyloid burden aggravated 5XFAD, tau both strains. At mechanistic level, resveratrol inhibited HFD-increased amyloidogenic processing precursor protein strains; it restored abnormal high levels proteolytic activity ubiquitin-proteasome system HFD, suggesting presence compensatory mechanism counteract accumulation aberrant proteins. Thus, our data suggest can correct harmful brain may be potential therapeutic agent obesity-related disorders pathology.