Peripheral Total Tau in Military Personnel Who Sustain Traumatic Brain Injuries During Deployment

Anlys Olivera, PhD¹; Natasha Lejbman, BS¹; Andreas Jeromin, PhD²; Louis M. French, PsyD^3,4; Hyung-Suk Kim, PhD¹; Ann Cashion, PhD¹; Vincent Mysliwiec, MD⁵; Ramon Diaz-Arrastia, MD, PhD^4,6; Jessica Gill, RN, PhD¹

¹National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland
²Quanterix Corporation, Lexington, Massachusetts
³Walter Reed National Military Medical Center, National Intrepid Center of Excellence, Bethesda, Maryland
⁴Center for Neuroscience and Regenerative Medicine, Bethesda, Maryland
⁵Madigan Army Medical Center, Tacoma, Washington
⁶Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland

ImportanceApproximately one-third of military personnel who deploy for combat operations sustain 1 or more traumatic brain injuries (TBIs), which increases the risk for chronic symptoms of postconcussive disorder, posttraumatic stress disorder, and depression and for the development of chronic traumatic encephalopathy. Elevated concentrations of tau are observed in blood shortly following a TBI, but, to our knowledge, the role of tau elevations in blood in the onset and maintenance of chronic symptoms after TBI has not been investigated.

ObjectivesTo assess peripheral tau levels in military personnel exposed to TBI and to examine the relationship between chronic neurological symptoms and tau elevations.

Design, Setting, and ParticipantsObservational assessment from September 2012 to August 2014 of US military personnel at the Madigan Army Medical Center who had been deployed within the previous 18 months. Plasma total tau concentrations were measured using a novel ultrasensitive single-molecule enzyme-linked immunosorbent assay. Classification of participants with and without self-reported TBI was made using the Warrior Administered Retrospective Casualty Assessment Tool. Self-reported symptoms of postconcussive disorder, posttraumatic stress disorder, and depression were determined by the Neurobehavioral Symptom Inventory, the Posttraumatic Stress Disorder Checklist Military Version, and the Quick Inventory of Depressive Symptomatology, respectively. Group differences in tau concentrations were determined through analysis of variance models, and area under the receiver operating characteristic curve determined the sensitivity and specificity of tau concentrations in predicting TBI and chronic symptoms. Seventy participants with self-reported TBI on the Warrior Administered Retrospective Casualty Assessment Tool and 28 control participants with no TBI exposure were included.

Main Outcomes and MeasuresConcentration of total tau in peripheral blood.

ResultsConcentrations of plasma tau were significantly elevated in the 70 participants with self-reported TBI compared with the 28 controls (mean [SD], 1.13 [0.78] vs 0.63 [0.48] pg/mL, respectively;F_1,97 = 4.97;P = .03). Within the self-reported TBI cases, plasma total tau concentrations were significantly associated with having a medical record of TBI compared with self-reported TBI only (mean [SD], 1.57 [0.92] vs 0.85 [0.52] pg/mL, respectively;F_1,69 = 6.15;P = .02) as well as reporting the occurrence of 3 of more TBIs during deployment compared with fewer than 3 TBIs (mean [SD], 1.52 [0.82] vs 0.82 [0.60] pg/mL, respectively;F_1,69 = 8.57;P = .008). The severity of total postconcussive symptoms correlated with total tau concentrations in the self-reported TBI group (r = 0.37;P = .003).

Conclusions and RelevanceMilitary personnel who report multiple TBIs have long-term elevations in total tau concentration. The total tau concentration relates to symptoms of postconcussive disorder

JAMA Neurol.2015;72(10):1109-1116. doi:10.1001/jamaneurol.2015.1383.