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

Charbel Moussa, Michaeline Hebron, Xu Huang, Jaeil Ahn, Robert A Rissman, Paul S Aisen, R Scott Turner, Charbel Moussa, Michaeline Hebron, Xu Huang, Jaeil Ahn, Robert A Rissman, Paul S Aisen, R Scott Turner

Abstract

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.

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

Figures

Fig. 1
Fig. 1
ELISA concentrations of a MMP9, b IL-4, c MDC, d FGF2, e Aβ42, and f Aβ40 in the CSF from patients treated with placebo (N = 19) or resveratrol (N = 19) for 52 weeks. Mean ± SD, p values and statistical methods are listed in Table 1
Fig. 2
Fig. 2
ELISA concentrations of a MMP10, b IL-1R4, c IL-12P40, d IL-12P70, e TNFα, and f RANTES in plasma from patients treated with placebo (N = 19) or resveratrol (N = 19) for 52 weeks. Mean ± SD, p values and statistical methods are listed in Table 2
Fig. 3
Fig. 3
Histograms represent a MMSE scores and b ADCS-ADL and c changes in ADL in placebo versus resveratrol groups in patients treated with placebo (N = 19) or resveratrol (N = 19) for 52 weeks. Mean ± SD, **p < 0.01, ***p < 0.001

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