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

TLDR

SIRT1 activation may be a viable target for treating or preventing neurodegenerative disorders. The study retrospectively analyzed CSF and plasma from 19 resveratrol‑treated and 19 placebo‑treated AD patients, using multiplex Xmap assays to quantify neurodegenerative markers and metalloproteinases. Resveratrol treatment over 52 weeks slowed cognitive decline, improved daily living scores, reduced CSF MMP9, increased anti‑inflammatory cytokines (MDC, IL‑4, FGF‑2), altered plasma MMP10 and pro‑inflammatory cytokines, and preserved CSF Aβ42 without affecting tau levels. ClinicalTrials.gov identifier NCT01504854.

Abstract

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. 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. 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. 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. ClinicalTrials.gov NCT01504854