Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults

Nathan A. Huebschmann, Teemu M. Luoto, Justin E. Karr, Ksenia Berghem, Kaj Blennow, Henrik Zetterberg, Nicholas J. Ashton, Joel Simrén, Jussi P. Posti, Jessica M. Gill, Grant L. Iverson

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26 Scopus citations

Abstract

Objective: Identification and validation of blood-based biomarkers for the diagnosis and prognosis of mild traumatic brain injury (mTBI) is of critical importance. There have been calls for more research on mTBI in older adults. We compared blood-based protein marker glial fibrillary acidic protein (GFAP) concentrations in serum and in plasma within the same cohort of older adults and assessed their ability to discriminate between individuals based on intracranial abnormalities and functional outcome following mTBI. Methods: A sample of 121 older adults [≥50 years old with head computed tomography (CT), n = 92] seeking medical care for a head injury [Glasgow Coma Scale scores of 14 (n = 6; 5.0%) or 15 (n = 115; 95.0%)] were enrolled from the emergency department (ED). The mean time between injury and blood sampling was 3.4 h (SD = 2.1; range = 0.5–11.7). Serum GFAP concentration was measured first using the Human Neurology 4-Plex Assay, while plasma GFAP concentration was later measured using the GFAP Discovery Kit, both on an HD-1 Single molecule array (Simoa) instrument. Glasgow Outcome Scale-Extended was assessed 1 week after injury. Results: Both serum and plasma GFAP levels were significantly higher in those with abnormal CT scans compared to those with normal head CT scans (plasma: U = 1,198, p < 0.001; serum: U = 1,253, p < 0.001). The ability to discriminate those with and without intracranial abnormalities was comparable between serum (AUC = 0.814) and plasma (AUC = 0.778). In the total sample, GFAP concentrations were considerably higher in plasma than in serum (Wilcoxon signed-rank test z = 0.42, p < 0.001, r = 0.42). Serum and plasma GFAP levels were highly correlated in the total sample and within all subgroups (Spearman's rho range: 0.826–0.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum: U = 1,625, p = 0.002; plasma: U = 1,539, p = 0.013). Neither plasma (AUC = 0.653) nor serum (AUC = 0.690) GFAP were adequate predictors of functional outcome 1 week after injury. Conclusions: Despite differences in concentration, serum and plasma GFAP levels were highly correlated and had similar discriminability between those with and without intracranial abnormalities on head CT following an mTBI. Neither serum nor plasma GFAP had adequate discriminability to identify patients who would have poor functional outcome.

Original languageEnglish
Article number1054
JournalFrontiers in Neurology
Volume11
DOIs
StatePublished - Sep 18 2020

Bibliographical note

Funding Information:
The authors acknowledge research assistant Anne Simi for her assistance with the patient enrolment and data collection, and research coordinator Annamari Aitolahti for her assistance with blood sample logistics. Funding. This study was financially supported by the Finnish State Research Funding, and the Finnish Medical Society Duodecim. TL and JP have received funding from Government's Special Financial Transfer tied to academic research in Health Sciences (Finland). JP has received funding from the Academy of Finland (#17379), Emil Aaltonen Foundation sr and the Finnish Brain Foundation sr. KB was supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). HZ was a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL.

Publisher Copyright:
© Copyright © 2020 Huebschmann, Luoto, Karr, Berghem, Blennow, Zetterberg, Ashton, Simrén, Posti, Gill and Iverson.

Keywords

  • computed tomography
  • glial fibrillary acidic protein
  • plasma
  • serum
  • traumatic brain injuries

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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