Plasma Tau and Amyloid Are Not Reliably Related to Injury Characteristics, Neuropsychological Performance, or White Matter Integrity in Service Members with a History of Traumatic Brain Injury

The aim of this study was to examine the relationship between plasma tau and amyloid beta-42 (A beta 42), neuropsychological functioning, and white matter integrity in U.S. military service members with (n = 155) and without (n = 42) a history of uncomplicated mild (n = 83), complicated mild (n = 26), or moderate, severe, or penetrating (n = 46) traumatic brain injury (TBI). We hypothesized that higher levels of tau and A beta 42 would be related to reduced neurocognitive performance and white matter integrity. Participants were enrolled prospectively from Walter Reed National Military Medical Center. Participants completed a blood draw, neuropsychological assessment, and diffusion tensor imaging (General Electric 3T) of the whole brain. From 20 neuropsychological test scores, five cognitive domain scores were computed. Measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated for 18 regions of interest (ROIs). There was no relationship found between the plasma biomarkers and neurocognitive performance in any of the three TBI groups (all ps >0.05; all R-2 changes <0.146). Although not reaching statistical significance after correction for multiple comparisons, higher tau and A beta 42 tended to be related to higher FA and lower MD, RD, and AD in patients with a history of moderate, severe, or penetrating TBI. There was no consistent relationship between either of the biomarkers and white matter integrity in the complicated and uncomplicated mild TBI groups. In addition, there was no significant relationship between the biomarkers and age, education, sex, race, bodily injury severity, time since injury, TBI severity, or number of TBIs (all ps >0.15). Future investigation in larger samples of moderate, severe, and penetrating TBI are needed. Other plasma biomarkers, including phosphorylated tau, exosomal tau, and interleukin-10, may be more promising measures to use in the diagnosis, management, and treatment of TBI.