Evidence map›Paper›PMID 38986050›Full record

SynthesisNeurology2024

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

Sarah Holper, Paula Loveland, Leonid Churilov, Dominic Italiano, Rosie Watson, Nawaf Yassi

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer's disease brain tissue.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  3. Pooled it
  4. Review
  5. Review
  6. Prognostic value of plasma %p-tau217 in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  8. Article
  9. Review
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  14. Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia-specific perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Sarah HolperFrom the Population Health and Immunity Division (S.H., P.L., R.W., N.Y.), The Walter and Eliza Hall Institute of Medical Research; Department of Medicine (S.H., P.L., L.C., D.I., R.W., N.Y.), The Royal Melbourne Hospital, and Department of Neurology (N.Y.), Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.ORCID 0000-0003-4257-964X
Paula LovelandFrom the Population Health and Immunity Division (S.H., P.L., R.W., N.Y.), The Walter and Eliza Hall Institute of Medical Research; Department of Medicine (S.H., P.L., L.C., D.I., R.W., N.Y.), The Royal Melbourne Hospital, and Department of Neurology (N.Y.), Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
Leonid ChurilovFrom the Population Health and Immunity Division (S.H., P.L., R.W., N.Y.), The Walter and Eliza Hall Institute of Medical Research; Department of Medicine (S.H., P.L., L.C., D.I., R.W., N.Y.), The Royal Melbourne Hospital, and Department of Neurology (N.Y.), Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.ORCID 0000-0002-9807-6606
Dominic ItalianoFrom the Population Health and Immunity Division (S.H., P.L., R.W., N.Y.), The Walter and Eliza Hall Institute of Medical Research; Department of Medicine (S.H., P.L., L.C., D.I., R.W., N.Y.), The Royal Melbourne Hospital, and Department of Neurology (N.Y.), Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
Rosie WatsonFrom the Population Health and Immunity Division (S.H., P.L., R.W., N.Y.), The Walter and Eliza Hall Institute of Medical Research; Department of Medicine (S.H., P.L., L.C., D.I., R.W., N.Y.), The Royal Melbourne Hospital, and Department of Neurology (N.Y.), Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
Nawaf YassiFrom the Population Health and Immunity Division (S.H., P.L., R.W., N.Y.), The Walter and Eliza Hall Institute of Medical Research; Department of Medicine (S.H., P.L., L.C., D.I., R.W., N.Y.), The Royal Melbourne Hospital, and Department of Neurology (N.Y.), Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.ORCID 0000-0002-0685-0060

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesNeuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD.

methodsMEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge

resultsThe search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, DISCUSSION: We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Indexed as

Alzheimer DiseaseAstrocytesBiomarkersChitinase-3-Like Protein 1Glial Fibrillary Acidic ProteinS100 Calcium Binding Protein beta SubunitCognitive DysfunctionHumansBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1GFAP protein, humanGlial Fibrillary Acidic ProteinS100B protein, humanS100 Calcium Binding Protein beta Subunit

Identifiers

PMID38986050
PMCPMC11314950

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.