Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion
Abstract
Objective: Reactive astrogliosis is a hallmark of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) but differences between the diseases and time course are unclear. Here, we used serum levels of the astroglial marker glial fibrillary acidic protein (GFAP) to investigate differences in patients with AD dementia, mild cognitive impairment (MCI)-AD and behavioural variant FTD (bvFTD). Methods: This multicentre study included serum samples from patients diagnosed with AD dementia (n=230), MCI-AD (n=111), bvFTD (n=140) and controls (n=129). A subgroup of patients with MCI-AD (n=32) was longitudinally followed-up for 3.9±2.6 years after sample collection. Serum levels of GFAP, neurofilament light chain (NfL) and pTau181 were measured by Simoa (Quanterix) and Ella (ProteinSimple). Results: In total, samples from 610 individuals from four clinical centres were investigated in this study. Serum GFAP levels in AD dementia were increased (median 375 pg/mL, IQR 276–505 pg/mL) compared with controls (167 pg/mL, IQR 108–234 pg/mL) and bvFTD (190 pg/mL, IQR 134–298 pg/mL, p<0.001). GFAP was already increased in the early disease phase (MCI-AD, 300 pg/mL, IQR 232–433 pg/mL, p<0.001) and was higher in patients with MCI-AD who developed dementia during follow-up (360 pg/mL, IQR 253–414 pg/mL vs 215 pg/mL, IQR 111–266 pg/mL, p<0.01, area under the curve (AUC)=0.77). Diagnostic performance of serum GFAP for AD (AUC=0.84, sensitivity 98%, specificity 60%, likelihood ratio 2.5) was comparable to serum pTau181 (AUC=0.89, sensitivity 80%, specificity 87%, likelihood ratio 6.0) but superior to serum NfL (AUC=0.71, sensitivity 92%, specificity 49%, likelihood ratio 1.8). Conclusions: Our data indicate a different type of reactive astrogliosis in AD and bvFTD and support serum GFAP as biomarker for differential diagnosis and prediction of MCI-to-dementia conversion.
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The more pronounced group differences in blood could suggest an association of GFAP levels with amyloidosis.
“The more pronounced group differences in blood could suggest an association of GFAP levels with amyloidosis [76–79].”
First cross-sectional results on GFAP showed less promising results as a suitable progression marker in genetic and sporadic bvFTD, since merely small changes in serum concentration of GFAP were detected.
“first cross-sectional results on glial fibrillary acidic protein (GFAP), suggesting to reflect reactive astrogliosis, showed less promising results as suitable progression marker in genetic and sporadic bvFTD, since merely small changes in serum concentration of GFAP were detected (cross-sectional) (Oeckl et al., 2022)”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Oeckl et al., 2022
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- Authors
- Oeckl, P., Anderl-Straub, S., Von Arnim, C. A. F., Baldeiras, I., Diehl-Schmid, J., Grimmer, T., Halbgebauer, S., Kort, A. M., Lima, M., Marques, T. M., Ortner, M., Santana, I., Steinacker, P., Verbeek, M. M., Volk, A. E., Ludolph, A. C., & Otto, M.
- Affiliations
- Universität Ulm (DE)
- Unidade Local de Saúde de Coimbra (PT)
- Technical University of Munich (DE)
- Radboud University Nijmegen (NL)
- University of Coimbra (PT)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Otto, Markus
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2022-04-27
- Volume
- 93
- Issue
- 6
- Pages
- 659-667
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W4225095672
- Cited by
- 94
- References
- 32
- Citations by year
- 2026: 10 · 2025: 33 · 2024: 30 · 2023: 18 · 2022: 3
- FWCI
- 13.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- German Federal Ministry of Education and Research (FTLDc 01GI1007A)
- Foundation of the state Baden-Württemberg (D.3830)
- Boehringer Ingelheim Ulm University BioCenter (D.5009)
- German Research Foundation/DFG (SFB1279)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- glial fibrillary acidic protein, serum biomarkers, Alzheimer's disease, frontotemporal dementia, behavioral variant frontotemporal dementia, mild cognitive impairment, reactive astrogliosis, neurofilament light chain, p-tau181, differential diagnosis, diagnostic accuracy, longitudinal follow-up, Simoa, ELISA
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