Emery, CarolynDebert, ChantelTabor, Jason Benjamin2023-04-142023-04-142023-04-13Tabor, J. B. (2023). Plasma biomarkers associated with sport-related concussion in adolescents: age and sex matter (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://prism.ucalgary.ca/handle/1880/116066https://dx.doi.org/10.11575/PRISM/dspace/40912Adolescent sport-related concussion (SRC) is a growing public health concern. Relative to adult SRC, there exists a large gap in the literature concerning adolescents, with few studies focusing on blood biomarkers relevant to SRC. Multiple studies in this thesis aim to increase our understanding of how blood biomarkers associated with SRC may present in athletic adolescents. This thesis begins by reviewing the current landscape of SRC biomarkers (i.e., glial fibrillary acidic protein [GFAP], ubiquitin-c-terminal hydrolase L1 [UCH-L1], neurofilament light [NF-L], and tau) and their possible roles in clinical management. Limitations to the SRC biomarker literature precluding their progress towards clinical validation are also highlighted. The neuroinflammatory response to concussion is then discussed in more detail, emphasizing potential covariables that may influence SRC biomarkers. Plasma biomarker levels [GFAP, UCH-L1, NF-L, total tau (T-tau), and P-tau-181] are then characterized with respect to age, sex, and previous concussion in healthy adolescents. This thesis then discusses the impact of replicate error in biomarker measurements at low concentrations and explores multiple biostatistical approaches to optimizing statistical precision in biomarker data analysis. Finally, the associations between SRC and plasma biomarker levels are examined in adolescent sport participants to investigate whether biomarkers are sensitive to SRC at various timepoints throughout recovery. The collective work of this thesis demonstrates that multiple confounding variables may influence GFAP, UCH-L1, NF-L, and tau in adolescents. First, in healthy individuals, UCH-L1 and P-tau-181 differed by sex, and age was negatively associated with GFAP. Secondly, this thesis showed that varying levels of agreement in these biomarkers samples from these healthy adolescents warranted a multilevel modelling approach using both replicates in analysis (as opposed to excluding sample duplicates based on arbitrary variation thresholds) to produce optimally precise estimates of association. Lastly, the work herein provides evidence suggesting GFAP, UCH-L1, NF-L, and T-tau are sensitive to SRC at various times throughout recovery in adolescents. Furthermore, results emphasize the importance of analyzing these biomarkers with respect to age and sex. The findings presented in this thesis make a significant contribution to the field of adolescent SRC biomarkers and support their continued use for investigating adolescent SRC neuropathophysiology.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Sport-related concussionBlood biomarkersAdolescentsSexTraumatic brain injuryNeuroscienceBiophysics--MedicalPhysiologyPathologydoctoral thesis