Journal of Neurology | June 25, 2022

Vasilevskaya A, Taghdiri F, Multani N, Ozzoude M, Tarazi A, Khodadadi M, Wennberg R, Rusjan P, Houle S, Green R, Colella B, Blennow K, Zetterberg H, Karikari T, Mikulis D, Hazrati LN, Kovacs GG, Davis KD, Tator C and Tartaglia MC

Journal of neurology. 2022

https://doi.org/10.1007/s00415-022-11223-7

This study was performed using the Quanterix HD-1 Analyzer.

This study was performed using Simoa Homebrew assay(s).

Abstract

Background

Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration.

Methods

Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging.

Results

Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08 pg/mL vs. 6.00 ± 2.53 pg/mL, respectively; 95% BCa CI 1.38–4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (β = − 0.002; 95% BCa CI − 0.003 to − 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10^–3 mm²/s vs. 0.90 ± 0.03 × 10^–3 mm²/s, p = 0.003; CC axial diffusivity: 1.49 ± 0.04 × 10^–3 mm²/s vs. 1.41 ± 0.02 × 10^–3 mm²/s, p < 0.001, respectively).

Conclusions

Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.