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J Neuroinflammation. 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.

Author information

1
Department of Neurology, Laboratory for Dementia and Parkinsonism, Translational Neurotherapeutics Program, National Parkinson's Foundation Center of Excellence, Georgetown University Medical Center, 4000 Reservoir Road, NW, Washington DC, 20057, USA. cem46@georgetown.edu.
2
Department of Neurology, Laboratory for Dementia and Parkinsonism, Translational Neurotherapeutics Program, National Parkinson's Foundation Center of Excellence, Georgetown University Medical Center, 4000 Reservoir Road, NW, Washington DC, 20057, USA.
3
Department of Neurology, Memory Disorders Program, Translational Neurotherapeutics Program, Georgetown University, Washington DC, USA.
4
Department of Biostatistics, Georgetown University Medical Center, 4000 Reservoir Road, NW, Washington DC, 20057, USA.
5
Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California, San Diego, CA, USA.
6
Alzheimer's Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, La Jolla, San Diego, CA, USA.

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

PMID:
28086917
PMCID:
PMC5234138
DOI:
10.1186/s12974-016-0779-0
[Indexed for MEDLINE]
Free PMC Article

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