ABSTRACT: This prospective cohort study examined the relationship between a panel of four serum proteomic biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], total Tau, and neurofilament light chain polypeptide [NF-L]) in 52 players from two different cohorts of male collegiate student football athletes from two different competitive seasons of Division I National Collegiate Athletic Association Football Bowl Subdivision. This study evaluated changes in biomarker concentrations (as indicators of brain injury) over the course of the playing season (pre- and post-season) and also assessed biomarker concentrations by player position using two different published classification systems. Player positions were divided into: 1) speed (quarterbacks, running backs, halfbacks, fullbacks, wide receivers, tight ends, defensive backs, safety, and linebackers) versus non-speed (offensive and defensive linemen), and 2) "Profile 1" (low frequency/high strain magnitudes positions including quarterbacks, wide receivers, and defensive backs), "Profile 2" (mid-range impact frequency and strain positions including linebackers, running backs, and tight ends), and "Profile 3" (high frequency/low strains positions including defensive and offensive linemen). There were significant increases in GFAP 39.3 to 45.6 pg/mL and NF-L 3.5 to 5.4 pg/mL over the course of the season (p < 0.001) despite only five players being diagnosed with concussion. UCH-L1 decreased significantly, and Tau was not significantly different. In both the pre- and post-season blood samples Tau and NF-L concentrations were significantly higher in speed versus non-speed positions. Concentrations of GFAP, Tau, and NF-L increased incrementally from "Profile 3," to "Profile 2" to "Profile 1" in the post-season. UCH-L1 did not. GFAP increased (by Profiles 3, 2, 1) from 42.4 to 49.6 to 78.2, respectively (p = 0.051). Tau increased from 0.37 to 0.61 to 0.67, respectively (p = 0.024). NF-L increased from 3.5 to 4.9 to 8.2, respectively (p < 0.001). Although GFAP and Tau showed similar patterns of elevations by profile in the pre-season samples they were not statistically significant. Only NF-L showed significant differences between profiles 2.7 to 3.1 to 4.2 in the pre-season (p = 0.042). GFAP, Tau, and NF-L concentrations were significantly associated with different playing positions with the highest concentrations in speed and "Profile 1" positions and the lowest concentrations were in non-speed and "Profile 3" positions. Blood-based biomarkers (GFAP, Tau, NF-L) provide an additional layer of injury quantification that could contribute to a better understanding of the risks of playing different positions.
