A1 Refereed original research article in a scientific journal
Association of acute blood biomarkers with diffusion tensor imaging and outcome in patients with traumatic brain injury presenting with GCS of 13–15
Authors: Mononen, Malla; Mohammadian, Mehrbod; Hossain, Iftakher; Roine, Timo; Tenovuo, Olli; Blennow, Kaj; Gill, Jessica; van Gils, Mark; Hutchinson, Peter; Luoto, Teemu M.; Maanpää, Henna-Riikka; Menon, David K.; Newcombe, Virginia F.J.; Raj, Rahul; Sanchez, Jean-Charles; Takala, Riikka S.K.; Tallus, Jussi; Zetterberg, Henrik; Posti, Jussi P.
Publisher: Elsevier BV
Publication year: 2026
Journal: NeuroImage: Clinical
Article number: 103934
Volume: 49
eISSN: 2213-1582
DOI: https://doi.org/10.1016/j.nicl.2025.103934
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://www.sciencedirect.com/science/article/pii/S2213158225002074?via%3Dihub
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/508402093
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
The aim of the study was to assess the association between blood-based biomarkers of different cellular origins and later white matter integrity, measured using post-acute diffusion tensor metrics, and their relation to outcome in patients presenting with Glasgow Coma Scale of 13–15 after traumatic brain injury (TBI).
Admission plasma samples for glial fibrillary acidic protein (GFAP), interleukin 10 (IL-10), heart fatty-acid binding protein (H-FABP), S100 calcium-binding protein B (S100B), total tau (T-tau), and amyloid beta 40 and 42 (Aβ40 and Aβ42) were taken for 92 patients. Diffusion-weighted magnetic resonance imaging (DW-MRI) and outcome evaluation was done ≥ 90 days post-injury. Outcome was assessed using Glasgow Outcome Scale-Extended (GOSE) and dichotomized as complete (GOSE 8) and incomplete (GOSE < 8) recovery. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized white matter tracts of the whole brain.
IL-10 and T-tau showed significant weak-moderate negative correlations with FA, and significant positive correlations with MD and RD in incompletely recovered patients. GFAP showed significant weak positive correlations with MD and RD, while its correlation with FA was slightly below significance threshold after correction for multiple comparison in incompletely recovered patients. Similar trends were observed in the whole cohort and in the CT-positive cohort, although these did not reach statistical significance.
Higher acute levels of GFAP, IL-10 and T-tau may be associated with the development of axonal injury. If validated in future studies, these biomarkers may help identify patients who require closer follow-up and DW-MRI.
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Funding information in the publication:
MMM is supported by the University of Turku Doctoral Programme, M. Mononen et al. NeuroImage: Clinical 49 (2026) 103934 9 the Finnish State Research Funding, the Finnish Medical Foundation, the Paulo Foundation, the Maire Taposen Foundation. KB is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer
Foundation (#AF-930351, #AF-939721 and #AF-968270), Hj¨ arnfonden, Sweden (#FO2017-0243 and #ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County
Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), and the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495). IH is supported by the Finnish Medical Foundation, the Paivikki ¨ and Sakari Sohlberg Foundation, the Paulo
Foundation, the Maire Taposen Foundation, the Orion Research Foundation and the Finnish Cultural Foundation. VFJN is supported by a National Institute of Health and Care Research (NIHR) Rostrees Trust Advanced Fellowship NIHR302544, which is funded in partnership by the NIHR and Rosetrees Trust. The views expressed are those of the author(s) and not necessarily those of the NIHR, Rosetrees Trust or the Department of Health and Social Care. HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356, #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21- 831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the European Partnership on Metrology, co-financed from the European Union’s Horizon Europe Research and Innovation Programme and by the Participating States (NEuroBioStand, #22HLT07), the Bluefield
Project, Cure Alzheimer’s Fund, the Olav Thon Foundation, the ErlingPersson Family Foundation, Familjen Ronstr ¨ oms ¨ Stiftelse, Stiftelsen for ¨ Gamla Tjanarinnor, ¨ Hjarnfonden, ¨ Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE),
the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, the UK Dementia Research Institute at UCL (UKDRI-1003), Siemens Healthineers, Germany, Novo Nordisk, Denmark, Prothena,
United States, Siemens, United States, Apellis, United States, Biogen, United States, Abbey United Kingdom. JPP is supported by the Research Council of Finland, Sigrid Jus´elius Foundation and Finnish State Research Funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the
manuscript. The authors thank the research nurses Patricia Bertenyi and Satu Honkala for their valuable contributions to this study. The results of this study were presented in Nordic Neurotrauma Conference in Lund, in October 2023 and in International Neurotrauma Society Conference in Cambridge, in September 2024.
