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

Christina Devoto, Rany Vorn, Sara Mithani, Timothy B. Meier, Chen Lai, Steven P. Broglio, Thomas McAllister, Christopher C. Giza, Daniel Huber, Jaroslaw Harezlak, Kenneth L. Cameron, Gerald McGinty, Jonathan Jackson, Kevin Guskiewicz, Jason P. Mihalik, Alison Brooks, Stefan Duma, Steven Rowson, Lindsay D. Nelson, Paul PasquinaChristine Turtzo, Lawrence Latour, Michael A. McCrea, Jessica M. Gill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: The 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. Methods: This 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. Results: Concentrations 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). Conclusion: These 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.

Original languageEnglish
Article number1202967
JournalFrontiers in Neurology
StatePublished - 2023
Externally publishedYes


  • brain trauma
  • concussion
  • mTBI
  • mild traumatic brain injury
  • p-tau181
  • sports related concussion


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