Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease.
Level 2 - randomized trial
Retrospective biomarker sub-study of a randomized controlled trial
PubMed 28086917 · doi:10.1186/s12974-016-0779-0
What was done
Researchers performed a retrospective sub-study analyzing banked cerebrospinal fluid (CSF) and plasma samples from a 52-week, multicenter, randomized controlled trial of oral resveratrol (up to 1 g twice daily) versus placebo in mild-to-moderate Alzheimer's disease. The analysis was restricted to 38 participants (19 resveratrol, 19 placebo) who had biomarker-confirmed Alzheimer's disease (baseline CSF Aβ42 < 600 ng/ml). Multiplex Xmap assays were used to measure markers of neurodegeneration and matrix metalloproteinases (MMPs) in CSF and plasma.
What was found
At 52 weeks compared to placebo, resveratrol reduced CSF MMP9 and increased CSF macrophage-derived chemokine (MDC), interleukin-4 (IL-4), and fibroblast growth factor-2 (FGF-2). Relative to baseline, resveratrol increased plasma MMP10 and decreased plasma IL-12P40, IL-12P70, and RANTES. Resveratrol also attenuated declines in Mini-Mental State Examination (MMSE) scores, ADCS-ADL scores, and CSF Aβ42 loss over 52 weeks relative to placebo, but did not alter CSF tau levels. Specific numerical values, confidence intervals, and p-values were not reported in the abstract.
Why it matters
These findings suggest that high-dose resveratrol can alter central and peripheral neuro-inflammatory and matrix metalloproteinase pathways while potentially slowing clinical progression in biomarker-confirmed Alzheimer's disease.
Limits
The study is a retrospective post-hoc analysis on a small sub-sample (N = 38) drawn from a larger trial. The abstract provides directional changes without reporting exact numerical values, effect sizes, or p-values. Tau pathology was not modified, and long-term clinical efficacy requires validation in adequately powered prospective phase III trials.
Cited by
- contradicts Phase 1 and Phase 2 clinical trials in Alzheimer's disease showed that resveratrol at doses of 500 mg or 1,000 mg daily reduced cerebrospinal fluid amyloid-beta 42 and improved cognitive function.