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

• Published in: Journal of neuroinflammation Vol. 14; no. 1; p. 1
• Main Authors: Moussa, Charbel, Hebron, Michaeline, Huang, Xu, Ahn, Jaeil, Rissman, Robert A., Aisen, Paul S., Turner, R. Scott
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.01.2017; BioMed Central
• Subjects: Activities of Daily Living; Adaptive Immunity - drug effects; Alzheimer Disease - complications; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - psychology; Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Analysis; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Care and treatment; Chemokine CCL5 - metabolism; Cognition Disorders - drug therapy; Cognition Disorders - etiology; Cytokines - metabolism; Dosage and administration; Double-Blind Method; Encephalitis - drug therapy; Encephalitis - etiology; Female; Fibroblast Growth Factor 2 - cerebrospinal fluid; Fibroblast growth factors; Follow-Up Studies; Humans; Inflammation; 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; United States; Interleukin-4; Macrophage-derived chemokine (MDC); Matrix metalloproteinase-(MMP)-9; Alzheimer; Resveratrol
• DOI: 10.1186/s12974-016-0779-0
• ISSN: 1742-2094

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. 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. 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. 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. ClinicalTrials.gov NCT01504854.