AUTHOR=Devoto Christina , Vorn Rany , Mithani Sara , Meier Timothy B. , Lai Chen , Broglio Steven P. , McAllister Thomas , Giza Christopher C. , Huber Daniel , Harezlak Jaroslaw , Cameron Kenneth L. , McGinty Gerald , Jackson Jonathan , Guskiewicz Kevin , Mihalik Jason P. , Brooks Alison , Duma Stefan , Rowson Steven , Nelson Lindsay D. , Pasquina Paul , Turtzo Christine , Latour Lawrence , McCrea Michael A. , Gill Jessica M. TITLE=Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts JOURNAL=Frontiers in Neurology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1202967 DOI=10.3389/fneur.2023.1202967 ISSN=1664-2295 ABSTRACT=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.