Demographics Essential in Analysis of Concussion-Related Serum Biomarkers

student athletes
student athletes
Healthy collegiate athletes express concussion-related serum biomarkers in variable concentrations; therefore, considering demographic factors such as sex and race is vital.

Healthy collegiate athletes express concussion-related serum biomarkers in variable concentrations and therefore accounting for such demographic factors as sex and race is essential, according to the results of an observational cohort study published in Neurology.

The investigators sought to describe the variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes and to report reliability metrics in a subsample of female athletes. Serum concentrations of the following biomarkers were analyzed: β-amyloid peptide 42 (Aβ42), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule-associated protein 2, and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase).

Levels of these biomarkers were measured in a total of 415 collegiate athletes without any recent exposure to head impact. The average age of the athletes was 19.0±1.2 years. Overall, 61% of the participants were men and 40% were white. Standardized normative distributions were reported for each of the biomarkers. The researchers assessed the main effects of sex and race, reporting demographic-specific normative metrics whenever appropriate. In a subset of 31 female participants, test-retest reliability and reliable change indices across a 6-month to 12-month interval were reported for Aβ42, total tau, S100B, and UCH-L1.

Men exhibited significantly higher UCH-L1 and S100B levels (P <.001 for both) compared with women, whereas women had significantly higher CNPase concentrations (P <.001). With respect to race, black participants exhibited significantly higher baseline levels of UCH-L1 and S100B (P <.001 for both) than white participants. In contrast, white participants had significantly higher baseline concentrations of Aβ42 (P =.005) and CNPase (P <.001).

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Test-retest reliability was poor overall, ranging from −0.02 to 0.40; Aβ42 increased significantly from time 1 to time 2.

The investigators concluded that because these study results suggest poor reliability for serum biomarkers among the healthy collegiate athletes who were evaluated, understanding how other factors influence biomarker expression, along with increased knowledge of reliable change metrics, may improve clinical interpretation and future study designs.


Asken BM, Bauer RM, DeKosky ST, et al. Concussion biomarkers assessed in collegiate student-athletes (BASICS) I: normative study. Neurology. 2018;91(23):e2109-e2122.