Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-analysis.

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.