Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease

Background: treatment of mild-moderate alzheimer's disease (ad) subjects (n = 119) for 52 weeks with the sirt1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in csf aβ40 levels and activities of daily living (adl) scores. methods: for this retrospective study,we examined banked csf and plasma samples from a subset of ad subjects with csf aβ42 <600 ng/ml (biomarker-confirmed ad) at baseline (n = 19 resveratrol-treated and n = 19 placebo-treated). we utilized multiplex xmap technology to measure markers of neurodegenerative disease and metalloproteinases (mmps) in parallel in csf and plasma samples. results: compared to the placebo-treated group,at 52 weeks,resveratrol markedly reduced csf mmp9 and increased macrophage-derived chemokine (mdc),interleukin (il)-4,and fibroblast growth factor (fgf)-2. compared to baseline,resveratrol increased plasma mmp10 and decreased il-12p40,il12p70,and rantes. in this subset analysis,resveratrol treatment attenuated declines in mini-mental status examination (mmse) scores,change in adl (adcs-adl) scores,and csf aβ42 levels during the 52-week trial,but did not alter tau levels. conclusions: collectively,these data suggest that resveratrol decreases csf mmp9,modulates neuro-inflammation,and induces adaptive immunity. sirt1 activation may be a viable target for treatment or prevention of neurodegenerative disorders. trial registration: clinicaltrials.gov nct01504854 © 2017 the author(s).