Serum Tau, Neurofilament Light Chain, Glial Fibrillary Acidic Protein, and Ubiquitin Carboxyl-Terminal Hydrolase L1 Are Associated with the Chronic Deterioration of Neurobehavioral Symptoms after Traumatic Brain Injury

The purpose of this study was to examine the association of serum tau, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCHL-1) concentrations evaluated within the first 12 months after a military-related TBI, with longitudinal changes in neurobehavioral functioning extending two or more years post-injury. Participants were 84 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center of Excellence/Traumatic Brain Injury Center 15-Year Longitudinal TBI Study, separated into three discreet groups: (a) uncomplicated mild TBI (MTBI; n = 28), (b) complicated mild, moderate, severe, and penetrating TBI combined (STBI; n = 29], and (c) non-injured controls (NIC, n = 27). Participants completed a battery of self-report neurobehavioral symptom measures (e.g., depression, post-traumatic stress disorder [PTSD], post-concussion, anxiety, somatic, cognitive, and neurological symptoms) within 12 months of injury (baseline), and then again at two or more years post-injury (follow-up). At baseline, participants also completed a blood draw to determine serum concentrations of tau, NFL, GFAP, and UCHL-1 using an ultra-sensitivity assay method. In the MTBI and STBI groups (using hierarchical regression analyses), (1) baseline tau concentrations predicted the deterioration of neurobehavioral symptoms from baseline to follow-up on measures of anxiety, PTSD, depression, post-concussion, somatic, and neurological symptoms (accounting for 10-28% of the variance); (2) NFL predicted the deterioration of depression, post-concussion, somatic, cognitive, and neurological symptoms (10-32% variance); (3) GFAP predicted the deterioration of post-concussion, PTSD, depression, anxiety, somatic, neurological, and cognitive symptoms (11-43% variance); and (4) UCHL-1 predicted the deterioration of anxiety, somatic, and neurological symptoms (10-16% variance). In the NIC group, no meaningful associations were found between baseline biomarker concentrations and the deterioration of neurobehavioral symptoms on the majority of measures. This study reports that elevated tau, NFL, GFAP, and UCHL-1 concentrations within the first 12 months of injury are associated with the deterioration of neurobehavioral symptoms that extends to the chronic phase of recovery after a TBI. These findings suggest that a blood-based panel including these biomarkers could be a useful prognostic tool to identifying those individuals at risk of poor future outcome after TBI.

Automated summary

This study examines the association between serum tau, NFL, GFAP, and UCHL-1 concentrations and longitudinal changes in neurobehavioral functioning after military-related TBI. The study finds that elevated concentrations of these biomarkers are associated with the deterioration of neurobehavioral symptoms, suggesting their potential as prognostic tools for identifying individuals at risk of poor outcome after TBI.