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Updated: Feb 5, 2026
Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI
Jessica Gill1, Lawrence Latour2, Ramon Diaz-Arrastia2
1From the National Institutes of Health (J.G., V.M., C.D.), National Institute of Nursing Research, the Center for Neuroscience and Regenerative Medicine (J.G., P.S.), Uniformed Services University of the Health Sciences, Biomarker Core, and the National Institutes of Health (L.L., C.T.), National Institute of Neurological Disorders and Stroke, Bethesda, MD; the Department of Neurology (R.D.-A.), University of Pennsylvania, Philadelphia, PA; the Department of Biomedical and Dental Sciences and Morphofunctional Imaging (S.M.), University of Messina, Italy; and the Quanterix Corporation (E.V., D.H., L.S., A.J.), Lexington, MA. gillj@mail.nih.gov.
Objectives:
To determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI).
Methods:
Study participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology.
Results:
Concentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (p's < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90-0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70-0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69-0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT.
Conclusion:
Our study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials.
Classification Of Evidence:
Class I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.
Insights
Glial fibrillary acidic protein (GFAP) and other blood biomarkers can identify mild traumatic brain injuries (mTBI) and associated neuroimaging findings. This blood test may aid in diagnosing mTBI and guiding medical decisions.
Area of Science:
- Neurology
- Biomarker Discovery
- Neurotrauma
Background:
- Mild traumatic brain injury (mTBI) diagnosis can be challenging, often requiring neuroimaging.
- Objective assessment of mTBI is crucial for appropriate patient management and stratification.
Purpose of the Study:
- To evaluate the efficacy of blood-based biomarkers in differentiating mTBI patients from healthy controls.
- To determine if these biomarkers can identify neuroimaging abnormalities (CT and MRI) in mTBI patients.
Main Methods:
- Plasma concentrations of GFAP, tau, UCH-L1, and NFL were measured in 277 mTBI patients and 49 healthy controls.
- Single-molecule array technology was employed for biomarker quantification.
- Statistical analyses, including AUC calculations, were used to assess diagnostic performance.
Main Results:
- GFAP, tau, and NFL levels were significantly elevated in mTBI patients compared to controls.
- GFAP demonstrated high discriminatory power for mTBI detection (AUC 0.93).
- GFAP also effectively identified intracranial findings on CT (AUC 0.77) and MRI abnormalities (AUC 0.83) in mTBI patients.
Conclusions:
- GFAP is a promising blood biomarker for detecting acute mTBI.
- A multimarker approach combining GFAP, tau, and NFL enhances diagnostic accuracy for mTBI subgroups.
- These biomarkers may assist in clinical decision-making and patient stratification in neurotrauma research.
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