阿尔茨海默病中的星形胶质细胞生物标志物：系统评价与荟萃分析
Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-analysis.
作者信息
Bellaver Bruna, Ferrari-Souza João Pedro, Uglione da Ros Lucas, Carter Stephen F, Rodriguez-Vieitez Elena, Nordberg Agneta, Pellerin Luc, Rosa-Neto Pedro, Leffa Douglas Teixeira, Zimmer Eduardo R
机构信息
From the Graduate Program in Biological Sciences: Biochemistry (B.B., J.P.F.-S., L.U.d.R., E.R.Z.), Department of Pharmacology (E.R.Z.), and Graduate Program in Biological Sciences: Pharmacology and Therapeutics (E.R.Z.), Universidade Federal do Rio Grande do Sul; Department of Psychiatry (S.F.C.), University of Cambridge; Wolfson Molecular Imaging Centre (S.F.C.), University of Manchester, UK; Department of Neurobiology (E.R.-V, A.N.), Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet (E.R.-V, A.N.); Theme Aging (A.N.), Karolinska University Hospital Stockholm, Stockholm, Sweden; Inserm U1082 (L.P.), Université de Poitiers, France; Translational Neuroimaging Laboratory (P.R.-N.), McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; McGill University (P.R.-N.), Montreal, Quebec, Canada; and ADHD Outpatient Program & Development Psychiatry Program (D.T.L.), Hospital de Clínicas de Porto Alegre, Brazil.
出版信息
Neurology. 2021 Jun 14;96(24):e2944-e2955. doi: 10.1212/WNL.0000000000012109.
OBJECTIVE
To perform a systematic review and meta-analysis to determine whether fluid and imaging astrocyte biomarkers are altered in Alzheimer disease (AD).
METHODS
PubMed and Web of Science databases were searched for articles reporting fluid or imaging astrocyte biomarkers in AD. Pooled effect sizes were determined with standardized mean differences (SMDs) using the Hedge G method with random effects to determine biomarker performance. Adapted questions from the Quality Assessment of Diagnostic Accuracy Studies were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42020192304).
RESULTS
The initial search identified 1,425 articles. After exclusion criteria were applied, 33 articles (a total of 3,204 individuals) measuring levels of glial fibrillary acidic protein (GFAP), S100B, chitinase-3-like protein 1 (YKL-40), and aquaporin 4 in the blood and CSF, as well as monoamine oxidase-B indexed by PET C-deuterium-l-deprenyl, were included. GFAP (SMD 0.94, 95% confidence interval [CI] 0.71-1.18) and YKL-40 (SMD 0.76, 95% CI 0.63-0.89) levels in the CSF and S100B levels in the blood (SMD 2.91, 95% CI 1.01-4.8) were found to be significantly increased in patients with AD.
CONCLUSIONS
Despite significant progress, applications of astrocyte biomarkers in AD remain in their early days. This meta-analysis demonstrated that astrocyte biomarkers are consistently altered in AD and supports further investigation for their inclusion in the AD clinical research framework for observational and interventional studies.
目的
进行一项系统评价和荟萃分析，以确定在阿尔茨海默病（AD）中，体液和影像学星形胶质细胞生物标志物是否发生改变。
方法
在PubMed和Web of Science数据库中检索报告AD中体液或影像学星形胶质细胞生物标志物的文章。采用随机效应的Hedge G方法，通过标准化均数差（SMD）确定合并效应量，以确定生物标志物的性能。应用诊断准确性研究质量评估中的改编问题进行质量评估。本研究方案先前已在PROSPERO注册（注册号：CRD42020192304）。
结果
初步检索确定了1425篇文章。应用排除标准后，纳入了33篇文章（共3204名个体），这些文章测量了血液和脑脊液中胶质纤维酸性蛋白（GFAP）、S100B、几丁质酶-3样蛋白1（YKL-40）和水通道蛋白4的水平，以及正电子发射断层扫描C-氘代-l-司来吉兰标记的单胺氧化酶-B。发现AD患者脑脊液中的GFAP（SMD 0.94，95%置信区间[CI] 0.71-1.18）和YKL-40（SMD 0.76，95%CI 0.63-0.89）水平以及血液中的S100B水平（SMD 2.91，95%CI 1.01-4.8）显著升高。
结论
尽管取得了显著进展，但星形胶质细胞生物标志物在AD中的应用仍处于早期阶段。这项荟萃分析表明，星形胶质细胞生物标志物在AD中持续发生改变，并支持进一步研究将其纳入AD临床研究框架，用于观察性和干预性研究。
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