Toxic tau: The TAU gene polymorphisms associate with concussion history in rugby union players

Concussion is a brain injury that occurs when biomechanical forces are transmitted to the head region resulting in neurological deficits. The accumulation of tau protein in autopsies of athletes with multiple concussions implicates tau in concussion-associated neurodegeneration. The TAU rs2435211 (C>T) and rs2435200 (G>A) polymorphisms are involved in pathological tau expression and neurodegenerative disease risk. The aims of this study were to investigate the associations of TAU (rs2435211, rs2435200) polymorphisms with concussion history and sustaining multiple concussions in rugby.

In total, 140 non-concussed controls and 163 previously concussed participants (all cases group, N=163; clinically diagnosed, N=140; multiple concussed, N=87) were recruited from high school (N=135, junior), club and professional rugby teams (N=166, senior).

Participants were genotyped for TAU rs2435211 and rs2435200 polymorphisms.

In seniors, the rs2435200 AA genotype was significantly over-represented in the control group compared to the multiple concussed subgroup (P=0.033, control: 25%, N=16, multiple concussed: 11%, N=6; OR: 0.34, 95% CI 0.12-0.96). While the AG genotype was significantly under-represented in the control compared to multiple concussed (P=0.024, control: 45%, N=29, multiple concussed: 63%, N=36; OR: 2.34, 95% CI 1.11-4.95). The inferred TAU (rs2435211 C>T-rs2435200 G>A) T-G haplotype was significantly under-represented in the control (19%, N=12) compared to the all cases group (30%, N=28, P=0.031).

The TAU-associated neurodegenerative pathway was implicated as a potential pathophysiological mechanism underlying concussion in seniors. In future, the identification of TAU polymorphisms associated with concussion risk may assist clinical management and reduce risk of severe complications.