GFAP as a biomarker in frontotemporal dementia and primary psychiatric disorders: diagnostic and prognostic performance
Abstract
Background Frontotemporal lobar degeneration (FTLD) and primary psychiatric disorders (PPD) are characterised by overlapping clinical features but different aetiologies. Here, we assessed for the first time the potential of blood glial fibrillar acidic protein (GFAP), marker of astrogliosis, as a discriminative and prognostic tool in FTLD and PPD. Methods The levels of GFAP in serum (sGFAP) of patients with FTLD (N=107) and PPD (N=44) and GFAP in whole blood samples (bGFAP) from FTLD (N=10), PPD (N=10) and healthy controls (N=18) were measured. We evaluated whether the sGFAP levels associate with C9orf72 repeat expansion, survival of FTLD and PPD patients, and brain atrophy assessed cross-sectionally and longitudinally by structural T1W MRI. We also examined the correlation between sGFAP and bGFAP levels in a subset of patients. Results sGFAP and bGFAP levels were elevated in the FTLD group compared with the PPD or control groups. Receiver operating characteristic analysis indicated an excellent diagnostic performance between FTLD and PPD (the area under the curve (AUC)=0.820, 95% CI 0.745 to 0.896). sGFAP and bGFAP levels showed a strong correlation and elevated sGFAP levels significantly associated with atrophy rate in the temporal cortex and predicted shorter survival time in patients with FTLD. No association with C9orf72 repeat expansion was detected. Conclusions sGFAP enabled differentiation of patients with FTLD and PPD and associated with shorter survival and more severe brain atrophy rate in patients with FTLD. These results suggest that blood-based GFAP represents a minimally invasive and useful biomarker in the differential diagnostics between patients with FTLD and PPD and in evaluating disease progression and astrogliosis in FTLD.
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Some studies reported elevated blood GFAP in participants with FTD compared to controls.
“Indeed, some studies reported elevated blood GFAP in participants with FTD compared to controls [8–18] but others observed no such GFAP increase in FTD [19–22].”
From Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders (2025) · cites this paper as [12]
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“Consistent with our findings, some studies found higher blood GFAP [12] and NfL [54, 55] to predict shorter survival in participants with FTD, whereas another study found no association of GFAP with risk of death [11].”
The role of neurofilament light in genetic frontotemporal lobar degeneration
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- Authors
- Katisko, K., Cajanus, A., Huber, N., Jääskeläinen, O., Kokkola, T., Kärkkäinen, V., Rostalski, H., Hartikainen, P., Koivisto, A. M., Hannonen, S., Lehtola, J.-M., Korhonen, V. E., Helisalmi, S., Koivumaa-Honkanen, H., Herukka, S.-K., Remes, A. M., Solje, E., & Haapasalo, A.
- Affiliations
- University of Eastern Finland (FI)
- Kuopio University Hospital (FI)
- University of Helsinki (FI)
- Oulu University Hospital (FI)
- Corresponding author
- Solje, Eino
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2021-06-29
- Volume
- 92
- Issue
- 12
- Pages
- 1305-1312
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W3176477588
- Cited by
- 65
- References
- 7
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 18 · 2023: 8 · 2022: 10 · 2021: 5
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sigrid Juséliuksen Säätiö (No grant number)
- Päivikki ja Sakari Sohlbergin Säätiö (No grant number)
- Yrjö Jahnssonin Säätiö (No grant number)
- Suomen Aivosäätiö (No grant number)
- Suomen Akatemia (315459, 315460)
- EU Horizon 2020, Marie Skłodowska-Curie grant agreement (740264)
- Suomen Lääketieteen Säätiö (3764)
- Maire Taposen Säätiö (No grant number)
- OLVI-Säätiö (No grant number)
- Instrumentariumin Tiedesäätiö (No grant number)
- Orionin Tutkimussäätiö (No grant number)
- Oulun Yliopisto (No grant number)
- Pohjois-Savon Rahasto (No grant number)
- Kuopion Yliopistollinen Sairaala (No grant number)
- Maud Kuistilan Muistosäätiö (No grant number)
- Academy of Finland (325022)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- glial fibrillary acidic protein, blood-based biomarkers, frontotemporal lobar degeneration, primary psychiatric disorders, differential diagnosis, astrocyte activation, C9orf72 repeat expansion, brain atrophy, survival prediction, disease progression
- MeSH terms
- Aged, Atrophy, Brain, Female, Glial Fibrillary Acidic Protein, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Sensitivity and Specificity, Biomarkers, Survival Rate, Disease Progression, Frontotemporal Dementia
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