Moussa Charbel, Hebron Michaeline, Huang Xu, Ahn Jaeil, Rissman Robert A, Aisen Paul S, Turner R Scott
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.
Department of Neurology, Memory Disorders Program, Translational Neurotherapeutics Program, Georgetown University, Washington DC, USA.
J Neuroinflammation. 2017 Jan 3;14(1):1. doi: 10.1186/s12974-016-0779-0.
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.
对119名轻度至中度阿尔茨海默病（AD）患者进行为期52周的治疗，使用SIRT1激活剂白藜芦醇（口服，每日两次，剂量高达1克），可减轻脑脊液Aβ40水平的逐渐下降以及日常生活活动（ADL）评分的下降。
在这项回顾性研究中，我们检测了基线时脑脊液Aβ42<600 ng/ml（生物标志物确诊的AD）的AD患者亚组的储存脑脊液和血浆样本（19名接受白藜芦醇治疗，19名接受安慰剂治疗）。我们利用多重Xmap技术同时测量脑脊液和血浆样本中的神经退行性疾病标志物和金属蛋白酶（MMPs）。
与安慰剂治疗组相比，在52周时，白藜芦醇显著降低了脑脊液MMP9水平，并增加了巨噬细胞衍生趋化因子（MDC）、白细胞介素（IL）-4和成纤维细胞生长因子（FGF）-2。与基线相比，白藜芦醇增加了血浆MMP10水平，并降低了IL-12P40、IL12P70和RANTES水平。在该亚组分析中，白藜芦醇治疗在52周试验期间减轻了简易精神状态检查（MMSE）评分、ADL（ADCS-ADL）评分变化和脑脊液Aβ42水平的下降，但未改变tau水平。
总体而言，这些数据表明白藜芦醇可降低脑脊液MMP9水平，调节神经炎症，并诱导适应性免疫。SIRT1激活可能是治疗或预防神经退行性疾病的一个可行靶点。
ClinicalTrials.gov NCT01504854。
