Repetitive head impact exposure and later-life plasma total tau in former National Football League players

Abstract

Introduction: Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former National Football League (NFL) players compared with controls and the relationship between RHI exposure and later-life plasma t-tau.

Methods: Ninety-six former NFL players (age 40-69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels. The cumulative head impact index (CHII) quantified RHI exposure. Subjects completed measures of clinical function.

Results: A higher CHII predicted greater plasma t-tau in the former NFL players (P = .0137). No group differences in plasma t-tau emerged, but a concentration ≥3.56 pg/mL was 100% specific to former NFL players. Plasma t-tau did not predict clinical function.

Discussion: Greater RHI exposure predicted higher later-life plasma t-tau concentrations, and further study on plasma t-tau as a candidate screening biomarker for CTE is warranted.

Keywords: American football; Chronic traumatic encephalopathy; Head trauma; Plasma; Repetitive head impacts; Tau; Total tau.

Fig. 1

Distribution of plasma total tau (t-tau) in former NFL players. There are no group differences in mean plasma t-tau. There is a significant difference in the range of plasma t-tau values (P = .042), and plasma t-tau levels above the black bolded line reflect those 100% specific to the former NFL players, which corresponds to ≥3.56 pg/mL. Y-axis values are plasma t-tau concentrations in pg/mL units.

Fig. 2

Greater exposure to repetitive head impacts is associated with higher later-life concentrations in plasma total tau (t-tau). The scatter plot depicts the relationship of the residuals between the cumulative head impact index (CHII) and plasma t-tau after controlling for age and body mass index, which was significant (P = .0137). Because the residuals resulted in negative values on the x-axis, a constant value was added to y- and x-axis values to facilitate interpretation. X-axis values are scores on the CHII, with higher scores representing greater exposure to repetitive head impact. Y-axis values are plasma t-tau concentrations in pg/mL units. Shaded region represents standard error.