c/mTBI affects 1.6 to 3.8 million athletes annually in the United States. Elevated levels of central nervous system proteins in blood and cerebrospinal fluid have been linked to c/mTBI and are being developed as biomarkers. The FDA has approved GFAP and UCH-L1 as diagnostic markers for c/mTBI. Characterizing the temporal profiles and interrelationships of additional biomarkers may further enhance their clinical utility for detection, treatment, and recovery monitoring.

Serum samples from 30 c/mTBI cases were collected at 1–4 hours and 8–16 hours post-injury and compared with 38 healthy controls. Biomarkers were measured using SIMOA^® Neurology 4-Plex D and p-Tau181 assays (Quanterix) and the Fujirebio ELISA S100B assay. Group comparisons, receiver operating characteristic (ROC) analysis, and correlation assessments were performed.

BD-Tau, NF-L, GFAP, UCH-L1, and S100B were significantly elevated at both post-injury time points compared with controls (p < 0.0008). p-Tau181 increases were not significant (p = 0.311 at 1–4h; p = 0.122 at 8–16h). ROC analyses demonstrated strong discriminatory power for BD-Tau, NF-L, GFAP, and UCH-L1 (AUC = 0.93–0.79) and moderate performance for S100B and p-Tau181 (AUC = 0.76–0.68). Correlations were strongest between BD-Tau and UCH-L1, NF-L, GFAP, and p-Tau181 (r = 0.47–0.70), while S100B correlated moderately with UCH-L1 (r = 0.42).

BD-Tau, NF-L, GFAP, UCH-L1, and S100B showed rapid and sustained elevation following c/mTBI, supporting their potential as diagnostic markers. Correlation patterns suggest complementary roles in neuronal and astroglial injury. Combined measurement may improve diagnostic accuracy, provide prognostic insights, and guide monitoring of recovery.