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Age- and Sex-Related Differences in GFAP and UCH-L1 Levels in Mild Traumatic Brain Injury
Celia Espinar-Barranco1,2,3, Gemma Álvarez-Corral2,3, María Del Rio-Rico2
1Programa de Doctorado en Bioquímica y Biología Molecular, University of Granada, 18016 Granada, Spain.
International Journal of Molecular Sciences
|June 12, 2026
Summary
Age and sex significantly impact blood biomarker levels for mild traumatic brain injury (mTBI). Adjusting cut-off values for glial fibrillary acidic protein (GFAP) and UCH-L1 improves diagnostic accuracy in mTBI patients.
Area of Science:
- Neuroscience
- Biomarkers
- Trauma Research
Background:
- Blood biomarkers like glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) aid in ruling out intracranial injury in mild traumatic brain injury (mTBI).
- Demographic factors, specifically age and sex, may influence the circulating levels of these biomarkers, potentially affecting their diagnostic utility.
- Optimizing the use of GFAP and UCH-L1 requires understanding and accounting for demographic variations in patient populations.
Purpose of the Study:
- To evaluate the impact of age and sex on GFAP and UCH-L1 concentrations in patients with mTBI.
- To assess whether adjusting biomarker cut-off values based on demographic factors enhances the diagnostic performance compared to head computed tomography (CT).
- To determine if demographic-adjusted cut-offs improve the accuracy of ruling out intracranial injury in diverse patient groups.
Main Methods:
- A retrospective observational study involving 820 consecutive mTBI patients presenting within 12 hours of injury.
- Measurement of GFAP and UCH-L1 concentrations using a chemiluminescent immunoassay.
- Analysis of biomarker levels stratified by age and sex, with derivation and evaluation of optimized cut-off values for diagnostic performance.
Main Results:
- GFAP concentrations showed significant variations with both age and sex, while UCH-L1 levels were primarily influenced by sex.
- Standard fixed cut-offs demonstrated reduced specificity in older patients, particularly for GFAP.
- Age-adjusted cut-offs improved specificity and maintained high negative predictive values across age groups, albeit with a slight decrease in sensitivity.
Conclusions:
- Age and sex are significant confounding factors for GFAP and UCH-L1 concentrations in mTBI patients.
- Demographic-adjusted cut-offs enhance diagnostic calibration and reduce false-positive classifications for intracranial injury.
- While sensitivity may be moderately reduced, adjusted cut-offs maintain high negative predictive values, improving the clinical utility of these biomarkers.
