@article{6849d8154529407e8a4a8a0bb7f8ea00,
title = "Are EPB41 and alpha-synuclein diagnostic biomarkers of sport-related concussion? Findings from the NCAA and Department of Defense CARE Consortium",
abstract = "Background: Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion. Methods: This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association–Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0–6 h post-injury) and after 6 h post-injury (7–48 h post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion. Results: A total of 140 athletes with concussion (79.3% males; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% males; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury. Conclusion: Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.",
keywords = "Biomarkers, College athletes, Concussion, Mild traumatic brain injury, Sport injury",
author = "{CARE Consortium Investigators} and Rany Vorn and Christina Devoto and Meier, {Timothy B.} and Chen Lai and Sijung Yun and Broglio, {Steven P.} and Sara Mithani and McAllister, {Thomas W.} and Giza, {Christopher C.} and Kim, {Hyung Suk} and Daniel Huber and Jaroslaw Harezlak and Cameron, {Kenneth L.} and Gerald McGinty and Jonathan Jackson and Guskiewicz, {Kevin M.} and Mihalik, {Jason P.} and Alison Brooks and Stefan Duma and Steven Rowson and Nelson, {Lindsay D.} and Paul Pasquina and McCrea, {Michael A.} and Gill, {Jessica M.}",
note = "Funding Information: TBM receives compensation as a member of the Clinical and Scientific Advisory Board for Quadrant Biosciences Inc. SPB has current or past research funding from the National Institutes of Health; Centers for Disease Control and Prevention; Department of Defense - USA Medical Research Acquisition Activity, National Collegiate Athletic Association; National Athletic Trainers{\textquoteright} Association Foundation; National Football League/Under Armour/GE; Simbex; and ElmindA. He has consulted for US Soccer (paid), US Cycling (unpaid), University of Calgary SHRed Concussions external advisory board (unpaid), medico-legal litigation, and received speaker honorarium and travel reimbursements for talks given. He is co-author of “Biomechanics of Injury (3rd edition)” and has a patent pending on “Brain Metabolism Monitoring Through Cytochrome-C-Oxidase (CCO) Measurements Using All-Fiber-Integrated Super-Continuum Source” (U.S. Application No. 17/164,490). JPM reports grants from National Collegiate Athletic Association and from Department of Defense during the conduct of the study; grants from National Institutes of Health, National Football League, Centers for Disease Control and Prevention outside the submitted work. MAM reports grants from Department of Defense and from National Collegiate Athletic Association during the conduct of the study. No other disclosures were reported. All the support had no involvement in the study design and writing of the manuscript or the decision to submit it for publication. Funding Information: The authors thank the research and medical staff at each of the CARE participation sites. This research was supported by the Grand Alliance CARE Consortium, funded in part by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DoD). This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Combat Casualty Care Research Program, endorsed by the Department of Defense, under Award No. W81XWH1420151. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the DoD. RV participated in the proteomics analysis, interpretation of data, and drafting of the manuscript; JMG, MAM, CCG, KLC, PP, SPB, JH, KMG, and TBM contributed to the study design and coordination and critical revision of the manuscript. All authors participated in the interpretation of data and critical revisions of the manuscript for important intellectual content. All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors. TBM receives compensation as a member of the Clinical and Scientific Advisory Board for Quadrant Biosciences Inc. SPB has current or past research funding from the National Institutes of Health; Centers for Disease Control and Prevention; Department of Defense - USA Medical Research Acquisition Activity, National Collegiate Athletic Association; National Athletic Trainers{\textquoteright} Association Foundation; National Football League/Under Armour/GE; Simbex; and ElmindA. He has consulted for US Soccer (paid), US Cycling (unpaid), University of Calgary SHRed Concussions external advisory board (unpaid), medico-legal litigation, and received speaker honorarium and travel reimbursements for talks given. He is co-author of “Biomechanics of Injury (3rd edition)” and has a patent pending on “Brain Metabolism Monitoring Through Cytochrome-C-Oxidase (CCO) Measurements Using All-Fiber-Integrated Super-Continuum Source” (U.S. Application No. 17/164,490). JPM reports grants from National Collegiate Athletic Association and from Department of Defense during the conduct of the study; grants from National Institutes of Health, National Football League, Centers for Disease Control and Prevention outside the submitted work. MAM reports grants from Department of Defense and from National Collegiate Athletic Association during the conduct of the study. No other disclosures were reported. All the support had no involvement in the study design and writing of the manuscript or the decision to submit it for publication. Funding Information: The authors thank the research and medical staff at each of the CARE participation sites. This research was supported by the Grand Alliance CARE Consortium, funded in part by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DoD). This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Combat Casualty Care Research Program, endorsed by the Department of Defense, under Award No. W81XWH1420151. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the DoD. Publisher Copyright: {\textcopyright} 2023",
year = "2023",
month = may,
doi = "10.1016/j.jshs.2022.11.007",
language = "English (US)",
volume = "12",
pages = "379--387",
journal = "Journal of Sport and Health Science",
issn = "2095-2546",
publisher = "Elsevier BV",
number = "3",
}