Evidence map›Paper›PMID 39289040›Full record

ReviewJournal of neurochemistry2025

The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.

Dea Gogishvili, Madison I J Honey, Inge M W Verberk, Lisa Vermunt, Elly M Hol, Charlotte E Teunissen, Sanne Abeln

Abstract readReview
In one paragraph

Review in Journal of neurochemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–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

26 citing papers in PubMed.

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  11. Unraveling the molecular mechanisms of aluminium chloride-induced Alzheimer's disease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
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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

7 authors.

Dea GogishviliBioinformatics, Computer Science Department, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-8809-0861
Madison I J HoneyNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0002-9422-8764
Inge M W VerberkNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0003-0341-7445
Lisa VermuntNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0001-7420-6384
Elly M HolDepartment of Translational Neuroscience, UMC Utrecht Brain Centre, University Medical Centre Utrecht, University Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-5604-2603
Charlotte E TeunissenNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0002-4061-0837
Sanne AbelnBioinformatics, Computer Science Department, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-2779-7174

Funding

European Commission (Marie Curie International Training Network 860197Health Holland, Topsector Life Sciences & Health LSHM20106ZonMw 73305095007
6 · The paper itself

Abstract

Glial fibrillary acidic protein (GFAP) is a well-established biomarker of reactive astrogliosis in the central nervous system because of its elevated levels following brain injury and various neurological disorders. The advent of ultra-sensitive methods for measuring low-abundant proteins has significantly enhanced our understanding of GFAP levels in the serum or plasma of patients with diverse neurological diseases. Clinical studies have demonstrated that GFAP holds promise both as a diagnostic and prognostic biomarker, including but not limited to individuals with Alzheimer's disease. GFAP exhibits diverse forms and structures, herein referred to as its proteoform complexity, encompassing conformational dynamics, isoforms and post-translational modifications (PTMs). In this review, we explore how the proteoform complexity of GFAP influences its detection, which may affect the differential diagnostic performance of GFAP in different biological fluids and can provide valuable insights into underlying biological processes. Additionally, proteoforms are often disease-specific, and our review provides suggestions and highlights areas to focus on for the development of new assays for measuring GFAP, including isoforms, PTMs, discharge mechanisms, breakdown products, higher-order species and interacting partners. By addressing the knowledge gaps highlighted in this review, we aim to support the clinical translation and interpretation of GFAP in both CSF and blood and the development of reliable, reproducible and specific prognostic and diagnostic tests. To enhance disease pathology comprehension and optimise GFAP as a biomarker, a thorough understanding of detected proteoforms in biofluids is essential.

Indexed as

BiomarkersGlial Fibrillary Acidic ProteinNervous System DiseasesAnimalsHumansProtein IsoformsProtein Processing, Post-TranslationalBiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinProtein IsoformsbiologybiomarkerGFAPimmunoassayproteoformstructure

Identifiers

PMID39289040
PMCPMC11658191

What OpenQuestion holds

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Registered trials

None linked

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.