Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts

Frontiers in Neurology

Neurology

Chen Lai¹  Paul Pasquina¹  Steven Rowson²  Stefan Duma²  Jaroslaw Harezlak³  Lindsay D. Nelson⁴  Michael A. McCrea⁴  Daniel Huber⁴  Timothy B. Meier⁴  Alison Brooks⁵  Thomas McAllister⁶  Christopher C. Giza⁷  Christina Devoto⁸  Kenneth L. Cameron⁹  Kevin Guskiewicz^1,10  Jason P. Mihalik^1,10  Steven P. Broglio^1,11  Lawrence Latour^1,12  Christine Turtzo^1,12  Rany Vorn^1,13  Jessica M. Gill^1,14  Sara Mithani^1,15  Gerald McGinty^1,16  Jonathan Jackson^1,16 

[1] Center for Neuroscience and Regenerative Medicine, Uniformed Services University and Health Science, Bethesda, MD, United States;Department of Biomedical Engineering, Virginia Tech, Blacksburg, VA, United States;Department of Epidemiology and Biostatistics School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States;Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States;Department of Orthopedics and Sports Medicine, University of Wisconsin, Madison, WI, United States;Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States;Departments of Pediatrics and Neurosurgery, UCLA Steve Tisch BrainSPORT Program, University of California, Los Angeles, Los Angeles, CA, United States;Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States;John A. Feagin Sports Medicine Fellowship, Keller Army Hospital, West Point, NY, United States;Matthew Gfeller Center, Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States;Michigan Concussion Center, University of Michigan, Ann Arbor, MI, United States;National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States;National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States;School of Nursing, Johns Hopkins University, Baltimore, MD, United States;School of Nursing, Johns Hopkins University, Baltimore, MD, United States;Department of Neurology, Johns Hopkins University, Baltimore, MD, United States;School of Nursing, University of Texas Health at San Antonio, San Antonio, TX, United States;United States Air Force Academy, Colorado Springs, CO, United States;

关键词: brain trauma;    p-tau181;    mild traumatic brain injury;    mTBI;    sports related concussion;    concussion;   

DOI  :  10.3389/fneur.2023.1202967

 received in 2023-04-09, accepted in 2023-07-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveThe aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes.MethodsThis pilot study comprised two independent cohorts. The first cohort—part of a Traumatic Head Injury Neuroimaging Classification (THINC) study—with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort—with a mean age of 19 years—comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay.ResultsConcentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690–0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT−/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT−/MRI−, n = 111) findings and UIC (P-values < 0.05).ConclusionThese findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

【 授权许可】

Unknown   
Copyright © 2023 Devoto, Vorn, Mithani, Meier, Lai, Broglio, McAllister, Giza, Huber, Harezlak, Cameron, McGinty, Jackson, Guskiewicz, Mihalik, Brooks, Duma, Rowson, Nelson, Pasquina, Turtzo, Latour, McCrea and Gill.