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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.
Glossary
- Aβ=
- amyloid-β;
- AD=
- Alzheimer disease;
- [11C]-DED=
- [11C]-deuterium-L-deprenyl;
- CI=
- confidence interval;
- CU=
- cognitively unimpaired;
- EOAD=
- early-onset AD;
- GFAP=
- glial fibrillary acidic protein;
- LOAD=
- late-onset AD;
- MAO-B=
- monoamine oxidase-B;
- NIA-AA=
- National Institute on Aging and Alzheimer's Association;
- NINCDS-ADRDA=
- National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association;
- SMD=
- standardized mean difference;
- YKL-40=
- chitinase-3-like protein 1
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received December 2, 2020.
- Accepted in final form March 19, 2021.
- © 2021 American Academy of Neurology
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