The Role of GFAP as a Marker of Astrocyte Activation in the Pathogenesis of Alzheimer's Dementia: A Literature Review

Komang Trisna Sumadewi

doi:10.47134/phms.v3i1.519

Authors

Komang Trisna Sumadewi Universitas Warmadewa

DOI:

https://doi.org/10.47134/phms.v3i1.519

Keywords:

GFAP, Astrocytes, Alzheimer's, Biomarker , Neuroinflammation

Abstract

This study aims to comprehensively review the role of glial fibrillary acidic protein (GFAP) as a marker of astrocyte activation in Alzheimer's disease (AD). The research utilized a descriptive-qualitative literature review approach by analyzing various current scientific sources, including indexed international journal articles, research reports, and relevant academic documents published between 2015 and 2025. Data collection involved systematic literature search techniques, followed by analysis comprising theme identification, data reduction, concept categorization, and inductive conclusion drawing to obtain a holistic understanding of the phenomenon under study. The study results show that GFAP plays a crucial role as a sensitive biomarker for astrocyte activation that occurs since the preclinical phase of Alzheimer's, demonstrating a strong correlation with amyloid-beta accumulation and the neuroinflammatory process. In addition to its function in early detection, GFAP is also capable of predicting the conversion of mild cognitive impairment (MCI) to Alzheimer's dementia with high diagnostic accuracy. Despite limitations in specificity and measurement variation, the integration of GFAP with other biomarkers such as pTau, NfL, and YKL-40 significantly enhances diagnostic validity and its potential for therapy monitoring. In conclusion, GFAP is a multifunctional biomarker that not only deepens our understanding of the mechanisms of reactive astrocytosis in AD pathogenesis but also provides new directions for the development of non-invasive diagnostics and more precise therapeutic strategies in neurodegenerative diseases.

References

Abraham, D.; P., P. (2024). A Methodological Framework for Descriptive Phenomenological Research. Western Journal of Nursing Research, 47. DOI: https://doi.org/10.1177/01939459241308071

Ally, M.; S., M.; Zetterberg, H.; Blennow, K.; Ashton, N.; Karikari, T.; Aparicio, H.; Frank, B.; Tripodis, Y.; Martin, B.; Palmisano, J.; Steinberg, E.; Simkin, I.; Farrer, L.; Jun, G.; Turk, K.; Budson, A.; O’Connor, M.; Au, R.; Goldstein, L.; Kowall, N.; Killiany, R.; Stern, R.; Stein, T.; McKee, A.; Qiu, W.; Mez, J.; Alosco, M. (2023). Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer’s disease. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 15. https://doi.org/10.1002/dad2.12492 DOI: https://doi.org/10.1002/dad2.12492

Bandaranayake, P. (2024). Application of grounded theory methodology in library and information science research: An overview. Sri Lanka Library Review. https://doi.org/10.4038/sllr.v38i2.70 DOI: https://doi.org/10.4038/sllr.v38i2.70

Bellaver, B.; F.-S., J.; Da Ros, L.; Carter, S.; Rodriguez-Vieitez, E.; Nordberg, A.; Pellerin, L.; Rosa-Neto, P.; Leffa, D.; Zimmer, E. (2021). Astrocyte Biomarkers in Alzheimer Disease. Neurology, 96. https://doi.org/10.1212/wnl.0000000000012109 DOI: https://doi.org/10.1212/WNL.0000000000012109

Bingham, A. (2023). From Data Management to Actionable Findings: A Five-Phase Process of Qualitative Data Analysis. International Journal of Qualitative Methods, 22. https://doi.org/10.1177/16094069231183620 DOI: https://doi.org/10.1177/16094069231183620

Chatterjee, P.; P., S.; Stoops, E.; Goozee, K.; Villemagne, V.; Asih, P.; Verberk, I.; Dave, P.; Taddei, K.; Sohrabi, H.; Zetterberg, H.; Blennow, K.; Teunissen, C.; Vanderstichele, H.; Martins, R. (2021). Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease. Translational Psychiatry, 11. DOI: https://doi.org/10.1038/s41398-020-01137-1

Cicognola, C.; J., S.; Hertze, J.; Zetterberg, H.; Blennow, K.; Mattsson-Carlgren, N.; Hansson, O. (2020). Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment. Alzheimer’s Research & Therapy, 13. https://doi.org/10.1186/s13195-021-00804-9 DOI: https://doi.org/10.21203/rs.3.rs-118286/v1

De Bastiani, M.; B., B.; Brum, W.; Souza, D.; Ferreira, P.; Rocha, A.; Povala, G.; Ferrari-Souza, J.; Benedet, A.; Ashton, N.; Karikari, T.; Zetterberg, H.; Blennow, K.; Rosa-Neto, P.; Pascoal, T.; Zimmer, E. (2023). Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies. Brain, Behavior, and Immunity, 110. DOI: https://doi.org/10.1016/j.bbi.2023.03.001

Doyle, L.; M., C.; Keogh, B.; Brady, A.; McCann, M. (2019). An overview of the qualitative descriptive design within nursing research. Journal of Research in Nursing, 25. DOI: https://doi.org/10.1177/1744987119880234

Ferrari-Souza, J.; F., P.; Bellaver, B.; Tissot, C.; Wang, Y.; Leffa, D.; Brum, W.; Benedet, A.; Ashton, N.; De Bastiani, M.; Rocha, A.; Therriault, J.; Lussier, F.; Chamoun, M.; Servaes, S.; Bezgin, G.; Kang, M.; Stevenson, J.; Rahmouni, N.; Pallen, V.; Poltronetti, N.; Klunk, W.; Tudorascu, D.; Cohen, A.; Villemagne, V.; Gauthier, S.; Blennow, K.; Zetterberg, H.; Souza, D.; Karikari, T.; Zimmer, E.; Rosa-Neto, P.; Pascoal, T. (2022). Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer’s disease. Molecular Psychiatry, 27. https://doi.org/10.1038/s41380-022-01716-2 DOI: https://doi.org/10.1101/2022.01.25.22269841

Fife, S.; G., J. (2024). Deductive Qualitative Analysis: Evaluating, Expanding, and Refining Theory. International Journal of Qualitative Methods, 23. https://doi.org/10.1177/16094069241244856 DOI: https://doi.org/10.1177/16094069241244856

Holper, S.; L., P.; Churilov, L.; Italiano, D.; Watson, R.; Yassi, N. (2024). Blood Astrocyte Biomarkers in Alzheimer Disease. Neurology, 103. https://doi.org/10.1212/wnl.0000000000209537 DOI: https://doi.org/10.1212/WNL.0000000000209537

Kim, K.; S., K.; Chang, K. (2023). GFAP as a Potential Biomarker for Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Cells, 12. DOI: https://doi.org/10.3390/cells12091309

Leipp, F.; V., J.; Mohaupt, P.; Coppens, S.; Jaffuel, A.; Niehoff, A.; Lehmann, S.; Hirtz, C. (2024). Glial fibrillary acidic protein in Alzheimer’s disease: A narrative review. Brain Communications, 6. https://doi.org/10.1093/braincomms/fcae396 DOI: https://doi.org/10.1093/braincomms/fcae396

Marksteiner, J.; H., C. (2025). Glial fibrillary acidic protein as a biomarker for diagnosis of Alzheimer’s disease in cerebrospinal fluid, plasma and saliva measured with Lumipulse technology: A narrative review. NeuroMarkers. https://doi.org/10.1016/j.neumar.2025.100038 DOI: https://doi.org/10.1016/j.neumar.2025.100038

Montoliu-Gaya, L., Alcolea, D., Ashton, N., Pegueroles, J., Levin, J., Bosch, B., Lantero-Rodríguez, J., Carmona‐Iragui, M., Wagemann, O., Balasa, M., Kac, P., Barroeta, I., Lladó, A., Brum, W., Videla, L., González-Ortiz, F., Benejam, B., Martínez, J., Karikari, T., … Fortea, J. (2023). Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: A longitudinal cohort study. EBioMedicine, 90, 104547. https://doi.org/10.1016/j.ebiom.2023.104547 DOI: https://doi.org/10.1016/j.ebiom.2023.104547

Oeckl, P., Anderl-Straub, S., Von Arnim, C., Baldeiras, I., Diehl-Schmid, J., Grimmer, T., Halbgebauer, S., Kort, A., Lima, M., Marques, T., Ortner, M., Santana, I., Steinacker, P., Verbeek, M., Volk, A., Ludolph, A., & Otto, M. (2022). Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion. Journal of Neurology, Neurosurgery, and Psychiatry, 93. DOI: https://doi.org/10.1136/jnnp-2021-328547

Ozcelikay-Akyıldız, G., Karadurmus, L., Çetinkaya, A., Uludağ, İ., Ozcan, B., Unal, M., Sezginturk, M., & Ozkan, S. (2024). The Evaluation of Clinical Applications for the Detection of the Alzheimer’s Disease Biomarker GFAP. Critical Reviews in Analytical Chemistry, 1–12. https://doi.org/10.1080/10408347.2024.2393874 DOI: https://doi.org/10.1080/10408347.2024.2393874

Pelkmans, W.; S., M.; Brugulat-Serrat, A.; Sánchez-Benavides, G.; Minguillón, C.; Fauria, K.; Molinuevo, J.; Grau-Rivera, O.; Escalante, A.; Kollmorgen, G.; Carboni, M.; Ashton, N.; Zetterberg, H.; Blennow, K.; Suárez-Calvet, M.; Gispert, J. (2023). Astrocyte biomarkers GFAP and YKL‐40 mediate early Alzheimer’s disease progression. Alzheimer’s & Dementia, 20. DOI: https://doi.org/10.1002/alz.13450

Pereira, J.; J., S.; Smith, R.; Mattsson-Carlgren, N.; Palmqvist, S.; Teunissen, C.; Zetterberg, H.; Stomrud, E.; Ashton, N.; Blennow, K.; Hansson, O. (2021). Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer’s disease. Brain, 144. https://doi.org/10.1093/brain/awab223 DOI: https://doi.org/10.1093/brain/awab223

Pratt, M. (2025). On the Evolution of Qualitative Methods in Organizational Research. Annual Review of Organizational Psychology and Organizational Behavior. https://doi.org/10.1146/annurev-orgpsych-111722-032953 DOI: https://doi.org/10.1146/annurev-orgpsych-111722-032953

Sánchez-Juan, P., Valeriano-Lorenzo, E., Ruiz-González, A., Pastor, A., Lara, H., López-González, F., Zea-Sevilla, M., Valentí, M., Frades, B., Ruiz, P., Saiz, L., Burgueño-García, I., Calero, M., Del Ser, T., & Rábano, A. (2024). Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles. Brain, 147. DOI: https://doi.org/10.1093/brain/awae035

Shen, J., Bu, F., Ye, Z., Zhang, M., Q., Yan, J., & Huang, T. (2024). Management of drug supply chain information based on “artificial intelligence + vendor managed inventory” in China: Perspective based on a case study. Frontiers in Pharmacology, 15. DOI: https://doi.org/10.3389/fphar.2024.1373642

Shen, X., Huang, S., Cui, M., Zhao, Q., Guo, Y., Huang, Y., Zhang, W., Chen, S., Zhang, Y., Chen, S., Chen, K., Cheng, W., Zuo, C., Tan, L., Ding, D., Dong, Q., Jeromin, A., Yen, T., & Yu, J. (2023). Plasma Glial Fibrillary Acidic Protein in the Alzheimer Disease Continuum: Relationship to Other Biomarkers, Differential Diagnosis, and Prediction of Clinical Progression. Clinical Chemistry. https://doi.org/10.1093/clinchem/hvad018 DOI: https://doi.org/10.1093/clinchem/hvad018

Shir, D., Graff‐Radford, J., Hofrenning, E., Lesnick, T., Przybelski, S., Lowe, V., Knopman, D., Petersen, R., Jack, C., Vemuri, P., Algeciras-Schimnich, A., Campbell, M., Stricker, N., & Mielke, M. (2022). Association of plasma glial fibrillary acidic protein (GFAP) with neuroimaging of Alzheimer’s disease and vascular pathology. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 14. https://doi.org/10.1002/dad2.12291 DOI: https://doi.org/10.1002/dad2.12291

Togia, A.; M., A. (2017). Research Methods in Library and Information Science. IntechOpen. https://doi.org/10.5772/intechopen.68749 DOI: https://doi.org/10.5772/intechopen.68749

Varma, V., An, Y., Kac, P., Bilgel, M., Moghekar, A., Loeffler, T., Amschl, D., Troncoso, J., Blennow, K., Zetterberg, H., Ashton, N., Resnick, S., & Thambisetty, M. (2024). Longitudinal progression of blood biomarkers reveals a key role of astrocyte reactivity in preclinical Alzheimer’s disease. medRxiv. https://doi.org/10.1101/2024.01.25.24301779 DOI: https://doi.org/10.1101/2024.01.25.24301779

Vila-Henninger, L., Dupuy, C., Van Ingelgom, V., Caprioli, M., Teuber, F., Pennetreau, D., Bussi, M., & Gall, C. (2022). Abductive coding: Theory building and qualitative (re)analysis. Sociological Methods & Research, 53. DOI: https://doi.org/10.1177/00491241211067508

Yang, Z., Sreenivasan, K., Strom, E., Osse, A., Pasia, L., Cosme, C., Mugosa, M., Chevalier, E., Ritter, A., Miller, J., Cordes, D., Cummings, J., & Kinney, J. (2023). Clinical and biological relevance of glial fibrillary acidic protein in Alzheimer’s disease. Alzheimer’s Research & Therapy, 15. DOI: https://doi.org/10.1186/s13195-023-01340-4