Article Text

Download PDFPDF
Original research
GFAP as a biomarker in frontotemporal dementia and primary psychiatric disorders: diagnostic and prognostic performance
  1. Kasper Katisko1,
  2. Antti Cajanus1,
  3. Nadine Huber2,
  4. Olli Jääskeläinen1,
  5. Tarja Kokkola1,
  6. Virve Kärkkäinen3,
  7. Hannah Rostalski2,
  8. Paivi Hartikainen3,
  9. Anne M Koivisto1,3,4,5,
  10. Sanna Hannonen1,3,
  11. Juha-Matti Lehtola1,
  12. Ville E Korhonen1,
  13. Seppo Helisalmi6,
  14. Heli Koivumaa-Honkanen7,8,
  15. Sanna-Kaisa Herukka1,3,
  16. Anne M Remes9,10,
  17. Eino Solje1,3,
  18. Annakaisa Haapasalo2
  1. 1Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland
  2. 2A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
  3. 3Neuro center, Neurology, Kuopio University Hospital, Kuopio, Finland
  4. 4Department of Internal Medicine and Rehabilitation, Geriatrics, Helsinki University Hospital, Helsinki, Finland
  5. 5Department of Neurosciences, University of Helsinki, Helsinki, Finland
  6. 6Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
  7. 7Institute of Clinical Medicine, Psychiatry, University of Eastern Finland, Kuopio, Finland
  8. 8Mental Health and Wellbeing Center, Kuopio University Hospital, Kuopio, Finland
  9. 9Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
  10. 10Medical Research Center, Oulu University Hospital, Oulu, Finland
  1. Correspondence to Dr Eino Solje, Institute of Clinical Medicine, Department of Neurology, University of Eastern Finland, Kuopio FI-70211, Finland; eino.solje{at}uef.fi

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.

  • frontotemporal dementia
  • MRI

Data availability statement

The datasets generated and analysed during the present study are available from the corresponding authors upon reasonable request.

Statistics from Altmetric.com

Data availability statement

The datasets generated and analysed during the present study are available from the corresponding authors upon reasonable request.

View Full Text

Footnotes

  • KK, AC and NH are joint first authors.

  • Twitter @SoljeEino

  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles