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Abstract
Objective To 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.
Methods In 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.
Results Males 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.
Conclusion Healthy 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.
Glossary
- Aβ42=
- β-amyloid peptide 42;
- BASICS=
- Biomarkers Assessed in Collegiate Student-Athletes;
- CNPase=
- 2′,3′-cyclic-nucleotide 3′-phosphodiesterase;
- CV=
- coefficient of variation;
- GFAP=
- glial fibrillary acidic protein;
- LLOQ=
- lower limit of quantification;
- LOD=
- limit of detection;
- MAP2=
- microtubule associated protein 2;
- RCI=
- reliable change index;
- S100B=
- S100 calcium binding protein B;
- SRC=
- sport-related concussion;
- UCH-L1=
- ubiquitin carboxy-terminal hydrolyzing enzyme L1;
- ULOQ=
- upper limit of quantification
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial page 1035
Articles page 1041
See page 1042
- Received December 1, 2017.
- Accepted in final form August 9, 2018.
- © 2018 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence
- Author response to Dr. Satyarthee
- Ideal concussion biomarker: Virtual or real existence
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