Concussion Biomarkers Assessed in Collegiate Student-Athletes (BASICS) I

Abstract

ObjectiveTo describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes.MethodsIn this observational cohort study, 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) serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Standardized normative distributions are reported for each biomarker. We evaluated main effects (analyses of variance) of sex and race, reporting demographic-specific normative metrics when appropriate. In a subset of 31 female participants, test-retest reliability (Pearson r) and reliable change indices (80%, 90%, and 95% confidence intervals) across a 6- to 12-month interval are reported for Aβ42, total tau, S100B, and UCH-L1.ResultsMales exhibited higher UCH-L1 (p < 0.001, Cohen d = 0.75) and S100B (p < 0.001, d = 0.56) than females, while females had higher CNPase (p < 0.001, d = 0.43). Regarding race, black participants had higher baseline levels of UCH-L1 (p < 0.001, d = 0.61) and S100B (p < 0.001, d = 1.1) than white participants. Conversely, white participants had higher baseline levels of Aβ42 (p = 0.005, d = 0.28) and CNPase (p < 0.001, d = 0.46). Test-retest reliability was generally poor, ranging from −0.02 to 0.40, and Aβ42 significantly increased from time 1 to time 2.ConclusionHealthy collegiate athletes express concussion-related serum biomarkers in variable concentrations. Accounting for demographic factors such as sex and race is essential. Evidence suggested poor reliability for serum biomarkers; however, understanding how other factors influence biomarker expression, as well as knowledge of reliable change metrics, may improve clinical interpretation and future study designs.

Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

“…Proteins produced in the brain after damage are detectable at extremely low concentrations in the plasma. Many of them suffer from proteolytic degradation in the blood, and their levels can be affected by the elimination of blood through the liver or kidneys [31]. All of these factors are critical for accurate diagnosis and for designing appropriate rehabilitation therapies.…”

“…All of these factors are critical for accurate diagnosis and for designing appropriate rehabilitation therapies. Recent studies have shown that healthy university athletes express serum biomarkers related to concussion in varying concentrations [31]. It is clear that serum biomarkers have high variability and, above all, demographic factors such as sex have not been considered.…”

Interactive Effects of Racial Identity and Repetitive Head Impacts on Cognitive Function, Structural MRI-Derived Volumetric Measures, and Cerebrospinal Fluid Tau and Aβ

“…Not everyone who is exposed to RHI will develop later-life neurological disorders. Previous fluid biomarker research by our team (Alosco et al, 2018c) and others (Asken et al, 2018b) emphasizes that other risk factors are likely at play, which may include those that occur more frequently in individuals with Black racial identity (e.g., CVD, low SES). In this study, the CHII only had an association with CSF p-tau 181 /t-tau ratio through its interaction with Black racial identity.…”

“…In the subset of football players, Black racial identity only predicted worse processing speed. Research among active collision sport athletes also provides evidence for racial identity as an independent correlate of serum concentrations of S100B, UCH-L1, and Aβ and cognitive test scores (Asken et al, 2018b).…”

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome

“…Aside from objectively assessing SRC presence, such markers have been suggested to predict and monitor recovery, while advancing our understanding of the underlying pathophysiological mechanisms of concussion ( 4 – 7 ). Nonetheless, there has been a preponderant focus on male athletes, and very few studies have explored sex-related variability of brain injury biomarkers and their relationships with the underlying neuropathological and clinical characteristics of SRC ( 8 , 9 ). This lack of biological data and the ensuing knowledge gap of the molecular drivers and processes associated with sex disparities following sports-concussion is a major obstacle to biomarker clinical translation.…”