Preliminary study of plasma exosomal tau as a potential biomarker for chronic traumatic encephalopathy

Background: Chronic traumatic encephalopathy (CTE) is a tauopathy associated with prior exposure to repetitive head impacts, such as those incurred through American football and other collision sports. Diagnosis is made through neuropathological examination. Many of the clinical features of CTE are common in the general population, with and without a history of head impact exposure, making clinical diagnosis difficult. As is now common in the diagnosis of other neurodegenerative disorders, such as Alzheimer's disease, there is a need for methods to diagnose CTE during life through objective biomarkers. Objective: The aim of this study was to examine tau-positive exosomes in plasma as a potential CTE biomarker. Methods: Subjects were 78 former National Football League (NFL) players and 16 controls. Extracellular vesicles were isolated from plasma. Fluorescent nanoparticle tracking analysis was used to determine the number of vesicles staining positive for tau. Results: The NFL group had higher exosomal tau than the control group (p ≤ 0.0001). Exosomal tau discriminated between the groups, with 82% sensitivity, 100% specificity, 100% positive predictive value, and 53% negative predictive value.Within the NFL group, higher exosomal tauwas associated withworse performance on tests of memory (p = 0.0126) and psychomotor speed (p = 0.0093). Conclusion: These preliminary findings suggest that exosomal tau in plasma may be an accurate, noninvasive CTE biomarker.