title: Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease.
abstract: 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.
authors.affiliation: 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.
authors.forename: Charbel
authors.identifier: 0000-0002-2012-7063
authors.initials: C
authors.lastname: Moussa
authors.affiliation: 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.
authors.forename: Michaeline
authors.initials: M
authors.lastname: Hebron
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Neurology, Memory Disorders Program, Translational Neurotherapeutics Program, Georgetown University, Washington DC, USA.
authors.forename: Jaeil
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Biostatistics, Georgetown University Medical Center, 4000 Reservoir Road, NW, Washington DC, 20057, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
authors.affiliation: Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Alzheimer's Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, La Jolla, San Diego, CA, USA.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Turner
mesh_terms: D000203:Activities of Daily Living; D056704:Adaptive Immunity / Q000187:drug effects*; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D018946:Chemokine CCL5 / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D016207:Cytokines / Q000378:metabolism*; D004311:Double-Blind Method; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000134:cerebrospinal fluid; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid; D008609:Mental Status Schedule; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018946:Chemokine CCL5; D016207:Cytokines; D010446:Peptide Fragments; D013267:Stilbenes; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol
keywords: Alzheimer; Interleukin-4; Macrophage-derived chemokine (MDC); Matrix metalloproteinase-(MMP)-9; Resveratrol