Elevated Serum Tau and UCHL-1 Concentrations Within 12 Months of Injury Predict Neurobehavioral Functioning 2 or More Years Following Traumatic Brain Injury: A Longitudinal Study

Objective: Blood-based biomarkers have received considerable attention for their diagnostic and prognostic value in the acute and postacute period following traumatic brain injury (TBI). The purpose of this study was to examine whether blood-based biomarker concentrations within the first 12 months of TBI can predict neurobehavioral outcome in the chronic phase of the recovery trajectory.

Setting: Inpatient and outpatient wards from 3 military medical treatment facilities.

Participants: A total of 161 service members and veterans classified into 3 groups: ( a ) uncomplicated mild TBI (MTBI; n = 37), ( b ) complicated mild, moderate, severe, penetrating TBI combined (STBI; n = 46), and ( c ) controls (CTRL; n = 78).

Design: Prospective longitudinal.

Main measures: Participants completed 6 scales from the Traumatic Brain Injury Quality of Life (ie, Anger, Anxiety, Depression, Fatigue, Headaches, and Cognitive Concerns) within 12 months (baseline) and at 2 or more years (follow-up) post-injury. Serum concentrations of tau, neurofilament light, glial fibrillary acidic protein, and UCHL-1 at baseline were measured using SIMOA.

Results: Baseline tau was associated with worse anger, anxiety, and depression in the STBI group at follow-up ( R2 = 0.101-0.127), and worse anxiety in the MTBI group ( R2 = 0.210). Baseline ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) was associated with worse anxiety and depression at follow-up in both the MTBI and STBI groups ( R2 Δ = 0.143-0.207), and worse cognitive concerns in the MTBI group ( R2 Δ = 0.223).

Conclusions: A blood-based panel including these biomarkers could be a useful tool for identifying individuals at risk of poor outcome following TBI.