Preliminary Study of Plasma Exosomal Tau as a Potential Biomarker for Chronic Traumatic Encephalopathy

Abstract

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 < .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 tau was associated with worse 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.

Injury cascades in TBI-related neurodegeneration

“…Blood and cerebrospinal fluid (CSF) markers of central nervous system (CNS) injury may also provide insight to pathophysiological outcomes of RSBT and multiple mTBI. A recent study found a higher number of tau-positive exosomes in former American football athletes compared to retired non-collision sport athletes 40 . Alosco et al reported a weak correlation between head impact exposure and plasma total tau levels, but no relationship with clinical outcomes 41 .…”

An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery

“…Furthermore, although the scope of the current study was to characterise blood biomarkers for the purpose of advancing our understanding of human secondary injury pathophysiology, the findings of the current study warrant future investigations to evaluate the clinical potential of PRDX-6 in SRC diagnosis and prognosis; competitively evaluating the statistical performance of this marker against other well-studied indices of brain injury such as s100B and GFAP may be useful. Recent evidence suggests that peripherally measured Tau in the systemic circulation may reflect CNS tauopathy (42,43) or axonal damage (44). While we did not observe differences in T-tau levels between athletes with SRC and controls in the subacute time period, higher blood concentrations were associated with SRC at medical clearance.…”

Telocytes and Their Extracellular Vesicles—Evidence and Hypotheses

“…Moreover, EVs seem to play an important role in several diseases, such as cancer, neurodegenerative, cardiovascular, and metabolic diseases [21,22,23,24,25,26]. …”