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

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; Eduardo R Zimmer

doi:10.1212/WNL.0000000000012109

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

Neurology. 2021 Jun 14;96(24):e2944-e2955. doi: 10.1212/WNL.0000000000012109.

Affiliations

¹ 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.
² 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. eduardo.zimmer@ufrgs.br.

PMID: 33952650
DOI: 10.1212/WNL.0000000000012109

Abstract

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 ¹¹C-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.