• Bruna Bellaver, João Pedro Ferrari-Souza, Lucas Uglione da Ros, Stephen F Carter, Elena Rodriguez-Vieitez, Agneta Nordberg, Luc Pellerin, Pedro Rosa-Neto, Douglas Teixeira Leffa, and Eduardo R Zimmer.
• Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
• Neurology. 2021 May 5.

ObjectiveTo perform a systematic review and meta-analysis to determine whether fluid and imaging astrocyte biomarkers are altered in Alzheimer's disease (AD).MethodsPubMed and Web of Science databases were searched for articles reporting fluid or imaging astrocyte biomarkers in AD. Pooled effect sizes were determined with mean differences (SMD) using the Hedge's G method with random-effects to determine biomarker performance. Adapted questions from QUADAS-2 were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42020192304).ResultsThe initial search identified 1,425 articles. After exclusion criteria were applied, 33 articles (a total of 3,204 individuals) measuring levels of GFAP, S100B, YKL-40 and AQP4 in the blood and cerebrospinal fluid (CSF), as well as MAO-B, indexed by positron emission tomography 11C-deuterium-L-deprenyl ([11C]-DED), were included. GFAP (SMD = 0.94; 95% CI = 0.71-1.18) and YKL-40 (SMD = 0.76; CI 95% = 0.63-0.89) levels in the CSF, S100B levels in the blood (SMD = 2.91; CI 95% = 1.01-4.8) were found significantly increased in AD patients.ConclusionsDespite significant progress, applications of astrocyte biomarkers in AD remain in their early days. The 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.© 2021 American Academy of Neurology.

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