Serum Dynamics of BD-Tau, NF-L, GFAP, UCH-L1, p-Tau181, and S100B as Diagnostic Biomarkers in Concussion and Mild Traumatic Brain Injury
Ahmed Chenna1, Brandon Yee1, Rao MORELAND2, Christos Petropoulos1
1Labcorp-Monogram Biosciences Inc, 2Labcorp-Esoterix
Objective:
To evaluate serum levels and temporal dynamics of brain-derived tau (BD-Tau), neurofilament light chain (NF-L), glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), phosphorylated tau at threonine 181 (p-Tau181), and S100B in concussion and mild traumatic brain injury (c/mTBI), and to assess their diagnostic and prognostic potential.
Background:

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.

Design/Methods:

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.

Results:

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).

Conclusions:

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.

10.1212/WNL.0000000000216679
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