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Review
. 2025 Dec;62(12):15576-15608.
doi: 10.1007/s12035-025-05219-3. Epub 2025 Jul 21.

The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression

Ekanayaka M S Bandara  1 , Prita R Asih  2   3 , Steve Pedrini  1   2 , Eugene Hone  1   2 , Warnakulasuriya Mary Ann Dipika Binosha Fernando  4   5 , Ralph N Martins  1   2   3
Affiliations
Review

The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression

Ekanayaka M S Bandara et al. Mol Neurobiol. 2025 Dec.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterised by neuropathological hallmarks, including extracellular amyloid plaques and neurofibrillary tangles. The disease is clinically defined by cognitive dysfunction, including learning, memory deficits, and behavioural changes. With the rising global prevalence of AD, early diagnosis is critical for implementing effective interventions before irreversible neuronal damage occurs. Biomarkers correlating amyloid deposition, tau pathology, neuroinflammation, and neurodegeneration are currently being investigated using cerebrospinal fluid analysis and positron emission tomography imaging. These methods are invasive or costly, limiting their widespread clinical utility. Blood-based biomarkers offer a promising alternative due to accessibility, cost-effectiveness, and feasibility for large-scale screening. Among blood-based biomarkers, plasma glial fibrillary acidic protein (GFAP) levels have gained interest in identifying individuals at risk of AD at preclinical stages. However, significant challenges remain, including methodological inconsistencies, analytical variability, and the need for standardisation across immunoassay platforms to ensure the clinical applicability of plasma GFAP measurement in AD diagnosis. Additionally, the specificity of GFAP for AD needs further evaluation, as increased plasma levels are also observed in other diseases. Similar issues are found with p-tau 217, the blood biomarker candidate for AD that has received the most attention. This review summarises the role of GFAP in the neuropathology of AD, provides evidence on plasma GFAP as an early blood biomarker for AD and identifies key knowledge gaps that need to be addressed. Future advancements in assay development and large-scale longitudinal studies are essential to validate its diagnostic and prognostic potential for community-based AD screening.

Keywords: AD; Alzheimer’s disease; Blood biomarkers; GFAP; GFAP isoforms; Glial fibrillary acidic protein.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
GFAP linear structure, functional domain, and isoforms (different colours of N and C terminal indicate alterations in domains) (created with BioRender.com); AD, Alzheimer’s disease; GFAP, glial fibrillary acidic protein
See this image and copyright information in PMC

References

    1. World Health Organization (2021) Global status report on the public health response to dementia. World Health Organization, Geneva
    1. Mertaş B, Boşgelmez I (2025) The role of genetic, environmental, and dietary factors in Alzheimer’s disease: a narrative review. Int J Mol Sci 26(3). 10.3390/ijms26031222 - PMC - PubMed
    1. Arora S, Santiago JA, Bernstein M, Potashkin JA (2023) Diet and lifestyle impact the development and progression of Alzheimer’s dementia. Front Nutr 10:1213223. 10.3389/fnut.2023.1213223 - DOI - PMC - PubMed
    1. Bloom GS (2014) Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol 71(4):505–508. 10.1001/jamaneurol.2013.5847 - DOI - PubMed
    1. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1(1):a006189. 10.1101/cshperspect.a006189 - DOI - PMC - PubMed

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