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

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Huebschmann, Nathan A., Luoto, Teemu M., Karr, Justin E., Berghem, Ksenia, Blennow, Kaj, Zetterberg, Henrik, Ashton, Nicholas J., Simrén, Joel +3 more·2020·Frontiers in Neurology
DOI 10.3389/fneur.2020.01054PMC PMC7530818
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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 hours (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 one 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<.001; serum: U=1,253, p<.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: .826-.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum: U=1,625, p=.002; plasma: U=1,539, p=.013). Neither plasma (AUC=0.653) nor serum (AUC=0.690) GFAP were adequate predictors of functional outcome one 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.

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  • Strong intraindividual correlations exist between serum and plasma NfL and GFAP.

    “While strong intraindividual correlations exist between serum and plasma NfL and GFAP,14–16 absolute values differ, preventing interchangeability.”

    From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [14]

    The Discussion (Plasma vs. Serum GFAP; page not provided) reports strong serum–plasma GFAP correlations, and the Results (Findings in the Total Sample; page not provided) report a systematic difference in their values. This paper does not establish the corresponding correlation or value difference for NfL, so it supports only the GFAP portion of the attributed claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Absolute values of serum and plasma NfL and GFAP differ, preventing interchangeability.

    “While strong intraindividual correlations exist between serum and plasma NfL and GFAP,14–16 absolute values differ, preventing interchangeability.”

    From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [14]

    The Results (Findings in the Total Sample; page not available) report a systematic difference between plasma and serum GFAP concentrations, supporting the concern that their absolute values cannot simply be exchanged. The cited paper does not report a serum–plasma NfL comparison, so it does not support extending the claim to NfL. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Systematic differences in absolute values and pre-analytic factors can influence serum and plasma measurements.

    “While within-person correlations between serum and plasma are typically strong, systematic differences in absolute values and pre-analytic factors can influence measurements.14–16,19”

    From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [14]

  • Most studies of NfL rely on serum.

    “Third, the inconsistent use of serum versus plasma further complicates comparisons, as most studies of NfL rely on serum.4,6,9,12–14”

    From Establishing demographic-based normative values for neurofilament light chain and glial fibrillary acidic protein in serum and plasma samples (2026) · cites this paper as [14]

    The Results and Discussion passages concern serum versus plasma GFAP, not the sample type used in most NfL studies. Searches for NfL and neurofilament light found individual studies in the References but no passage assessing whether most NfL studies rely on serum. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Huebschmann, N. A., Luoto, T. M., Karr, J. E., Berghem, K., Blennow, K., Zetterberg, H., Ashton, N. J., Simrén, J., Posti, J. P., Gill, J. M., & Iverson, G. L.
Affiliations
  • Spaulding Rehabilitation Hospital (US)
  • Tampere University Hospital (FI)
  • Harvard University (US)
  • Sahlgrenska University Hospital (SE)
  • National Health Service (GB)
  • University of Turku (FI)
  • National Institutes of Health (US)
Corresponding author
Iverson, Grant L.
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2020-09-18
Volume
11
Pages
1054-1054
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2020.01054
PMC
PMC7530818
OpenAlex
W3088667180
Cited by
85
References
2
Citations by year
2026: 12 · 2025: 20 · 2024: 10 · 2023: 14 · 2022: 18 · 2021: 10 · 2020: 1
FWCI
7.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UTUPub (University of Turku) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Tampere University Institutional Repository (Tampere University) (submittedVersion, cc-by)
Funders
  • Alzheimer's Drug Discovery Foundation (2016862, FO2017-0243, 201809, 2017-00915, #ALFGBG-715986, 201809–2016862, JPND2019-466-236, 201809-2016615, #RDAPB‐201809‐2016615, AF-742881)
  • Finska Läkaresällskapet
  • EU Joint Programme – Neurodegenerative Disease Research (JPND2019-466-236)
  • European Commission (201809-2016862, JPND2019‐466‐236)
  • Hjärnfonden (FO2017‑0243, FO2017, ALFGBG-715986, JPND2019-466-236)
  • Vetenskapsrådet (2017-00915, (#ALFGBG-715986, -201809-2016615, 201809-2016862, 681712, 02532, 2018-, JPND2019-466-236, ALFGBG-720931, FO2017-0243, 2018-02532)
  • Emil Aaltosen Säätiö
  • Suomalainen Lääkäriseura Duodecim
  • UK Dementia Research Institute (JPND2019-466–236, #2017-00915, ALFGBG-715986, RDAPB-201809-2016615, FO2017-0243, -0243, -201809-2016615, -715986)
  • H2020 European Research Council (681712)
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords
glial fibrillary acidic protein, mild traumatic brain injury, older adults, serum biomarkers, plasma biomarkers, blood-based biomarkers, intracranial abnormalities, functional outcome, Glasgow Outcome Scale-Extended, head CT, diagnostic accuracy, prognostic factors, Simoa single molecule array, biomarker validation

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