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.
- frontotemporal dementia
Data availability statement
The datasets generated and analysed during the present study are available from the corresponding authors upon reasonable request.
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KK, AC and NH are joint first authors.
KK, AC and NH contributed equally.
ES and AH contributed equally.
Contributors KK, AC, NH, ES, OJ, AH, S-KH and AMR designed the study, analysed and interpreted the data, wrote and revised the manuscript. AMK, J-ML, VK, HR, TK, PH, SHa,SHe, VEK and HK-H contributed to data acquisition, data interpretation and revision of the manuscript. All authors approved the manuscript prior to submission.
Funding This study has received funding from Finnish Medical Foundation (KK, grant number 3764), Finnish Alzheimer’s Disease Research Society (KK, no grant number), Olvi Foundation (KK, no grant number), Maire Taponen foundation (KK, no grant number), Päivikki and Sakari Sohlberg Foundation (AH, no grant number), Yrjö Jahnsson Foundation (AH, no grant number), Finnish Cultural Foundation (KK, no grant number), Maud Kuistila Memorial Foundation (KK, AC, no grant number), Finnish Brain Foundation (ES, KK, AC, no grant number), Orion Research Foundation (ES, no grant number), Instrumentarium Science Foundation (ES, no grant number), Sigrid Jusélius Foundation (ES, no grant number), University of Oulu (no grant number), Kuopio University Hospital (no grant number), Academy of Finland [grant nos. 315 459 (AH) and 315 460 (AH)], and Academy of Finland, PROFI5, grant number 325 022 (SH). This publication is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 740 264. NH and HR are PhD students in the UEF Doctoral Programmes of Molecular Medicine (DPMM) and GenomMed, respectively. This study is part of the FinFTD network research activities.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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