ObjectiveTo evaluate changes in serum biomarker concentrations (β-amyloid peptide 42 [Aβ₄₂], total tau, ubiquitin carboxy-terminal hydrolyzing enzyme L1, S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], microtubule associated protein 2 [MAP2], and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase [CNPase]) after sport-related concussion (SRC) in a sample of collegiate athletes. Associations with clinical outcomes were also investigated.MethodsParticipants in this case-control study included 36 athletes (50% male, 61% white, aged 19.7 ± 1.0 years) with SRC. Twenty-nine also had baseline blood drawn, allowing for within-patient analyses of concentration changes. Between-group analyses incorporated 86 demographically matched controls (51% male, 63% white, aged 19.6 ± 1.1 years). Biomarker sensitivity/specificity for SRC vs controls and relative to standardized normative cutoffs was evaluated (receiver operating characteristics). We also analyzed associations between post-SRC clinical outcomes and both biomarker change from baseline and post-SRC concentrations.ResultsThe majority of blood samples had concentrations of GFAP, MAP2, and CNPase below limits of quantification. Within-patient analyses indicated elevated S100B after SRC (p = 0.003, 67% of patients elevated), especially for blood samples collected <4 hours post-SRC (88% of patients). Significant between-group differences were limited to blood draws <4 hours post-SRC: Aβ₄₂ (81% of SRC > control median, area under the curve [AUC] = 0.75 [95% confidence interval 0.59–0.91]), total tau (75% SRC > control, AUC = 0.74 [0.56–0.79]), and S100B (88% SRC > control; AUC [specific to white race] = 0.82 [0.72–0.93]). Using standardized normative cutoffs (z > 1.0), specificity ranged from 79.1% to 89.3% while sensitivity was <70%. Biomarkers were not associated with clinical outcomes.ConclusionFor SRC, diagnostic accuracy of serum biomarkers appears best if blood is collected within a few hours. Accurate blood marker identification of SRC appears somewhat dependent on the “healthy” comparison. Additional research must evaluate whether physiologic changes in the absence of clinical changes, or vice versa, are relevant for concurrent or future neurologic health.Classification of evidenceThis study provides Class III evidence that certain serum biomarkers are elevated from baseline and higher than demographically matched controls after sport-related concussion.