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

J Neuroinflammation. 2017 Jan 3;14(1):1. doi: 10.1186/s12974-016-0779-0.


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: NCT01504854.

Keywords: Alzheimer; Interleukin-4; Macrophage-derived chemokine (MDC); Matrix metalloproteinase-(MMP)-9; Resveratrol.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Activities of Daily Living
  • Adaptive Immunity / drug effects*
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Chemokine CCL5 / metabolism
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology
  • Cytokines / metabolism*
  • Double-Blind Method
  • Encephalitis / drug therapy*
  • Encephalitis / etiology
  • Female
  • Fibroblast Growth Factor 2 / cerebrospinal fluid
  • Follow-Up Studies
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / cerebrospinal fluid
  • Mental Status Schedule
  • Peptide Fragments / cerebrospinal fluid
  • Resveratrol
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use*
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Chemokine CCL5
  • Cytokines
  • Peptide Fragments
  • Stilbenes
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Fibroblast Growth Factor 2
  • Matrix Metalloproteinase 9
  • Resveratrol

Associated data