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

Resveratrol Regulates Neuro-Inflammation and Induces Adaptive Immunity in Alzheimer's Disease

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Free PMC article
Clinical Trial

Resveratrol Regulates Neuro-Inflammation and Induces Adaptive Immunity in Alzheimer's Disease

Charbel Moussa et al. J Neuroinflammation. .
Free PMC article

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

Comment in

  • Resveratrol for Alzheimer's disease?
    Martin I. Martin I. Sci Transl Med. 2017 Feb 1;9(375):eaam6055. doi: 10.1126/scitranslmed.aam6055. Epub 2017 Feb 1. Sci Transl Med. 2017. PMID: 28148845

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References

    1. Pasinetti GM, Wang J, Ho L, Zhao W, Dubner L. Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochim Biophys Acta. 2015;1852:1202–1208. doi: 10.1016/j.bbadis.2014.10.006. - DOI - PMC - PubMed
    1. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, Rissman RA, Raman R, Aisen PS, Alzheimer’s Disease Cooperative S A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85:1383–1391. doi: 10.1212/WNL.0000000000002035. - DOI - PMC - PubMed
    1. Fox NC, Black RS, Gilman S, Rossor MN, Griffith SG, Jenkins L, Koller M, Study AN. Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology. 2005;64:1563–1572. doi: 10.1212/01.WNL.0000159743.08996.99. - DOI - PubMed
    1. De Stefano N, Airas L, Grigoriadis N, Mattle HP, O’Riordan J, Oreja-Guevara C, Sellebjerg F, Stankoff B, Walczak A, Wiendl H, Kieseier BC. Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs. 2014;28:147–156. doi: 10.1007/s40263-014-0140-z. - DOI - PubMed
    1. Vafadari B, Salamian A, Kaczmarek L. MMP-9 in Translation: From Molecule to Brain Physiology, Pathology and Therapy. J Neurochem. 2016;139(Suppl 2):91–114. - PubMed

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