ArticleInternational journal of molecular sciences2026
Age- and Sex-Related Differences in GFAP and UCH-L1 Levels in Mild Traumatic Brain Injury.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) are increasingly used to rule out intracranial injury in patients with mild traumatic brain injury (mTBI); however, their circulating levels may be influenced by demographic factors. This study evaluated the effects of age and sex on GFAP and UCH-L1 concentrations and assessed whether adjusted cut-off values improve the diagnostic performance of head computed tomography (CT). In this retrospective observational study, 820 consecutive patients with mTBI presenting within 12 h of injury underwent CT imaging and biomarker measurements using a chemiluminescent immunoassay. CT-positive findings were identified in 11.8% of patients (n = 97). Biomarker levels were analyzed according to age and sex, and optimized cut-off values were derived and evaluated. GFAP concentrations varied significantly according to both age and sex, whereas UCH-L1 demonstrated mainly sex-related differences. The use of manufacturer-recommended fixed cut-offs resulted in markedly reduced specificity in older patients, particularly for GFAP. Age-adjusted cut-offs improved specificity while maintaining high negative predictive values across all age groups, although this was accompanied by a reduction in sensitivity and an increase in false-negative results. For the combined GFAP/UCH-L1 assay, sensitivity ranged from 90.9% to 100%, specificity from 42.6% to 57.0%, and negative predictive values from 97.7% to 100%. Age-adjusted cut-off values for GFAP ranged from 82.1 to 112.2 pg/mL across adult age groups, whereas age-adjusted UCH-L1 cut-off values ranged from 469.6 to 1072.5 pg/mL. In conclusion, age and sex significantly influence GFAP and UCH-L1 concentrations in mTBI patients. Demographic-adjusted cut-offs improve diagnostic calibration and reduce false-positive classifications while maintaining high negative predictive values despite a moderate reduction in sensitivity.
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