Non-concussive Repetitive Head Impacts and Intense Physical Activity Elevate pT181-Tau and pT181/total-Tau in Plasma of Young Adults

Abstract

ABSTRACTIMPORTANCEHead impacts resulting in traumatic brain injury (TBI) lead to elevation of phosphorylated tau protein in plasma, the biomarkers for patients with acute and chronic TBI. Dynamics of phosphorylated tau protein level (pTau) and ratio of pTau and total tau in subjects after the non-concussive head impact was not yet investigated.OBJECTIVETo determine the acute effect of repetitive low-intensity head impacts on phosphorylated and total tau protein levels in plasma of young adults and to assess the effect of the head impacts on focused attention and cognitive flexibility.DESIGNThe study cohort consisted of young professional soccer players performing intense physical activity without heading the ball (n=32) and physical activity including the heading (n=28).SETTINGThe effect of repetitive non-concussive head impacts was monitored in all athletes evaluating the parameters of physical activity, impact force during heading the ball, together with neuropsychological testing of cognitive attention and cognitive flexibility at multiple time-points before and during a set of controlled training exercises. The total and phosphorylated tau protein levels were determined using an ultrasensitive single molecule assay at 3 time points: before training, 1 h, and 24 h after each training session in a non-fasting state. The psychological scores were collected before and 1 h after the training using Trail Making Test.PARTICIPANTSThe study included volunteer male college soccer players. The eligible participants were selected based on the similar demographic variables, such as age, years of performing organized sport, weekly sport activity and body mass index. The subjects with the history of previous TBI were excluded from the study.MAIN OUTCOMES AND MEASURESThe primary study outcomes are the levels of total tau protein and tau protein phosphorylated at the Threonine 181 in plasma samples, and cognitive status of the study participants. The study hypothesis was formulated before the data collection.RESULTSWe found significantly elevated levels of total tau and phospho-tau protein (pT181) in the plasma of soccer players one hour after physical exercise (Tau: 1.35-fold, 95% CI 1.2-1.5,P= .0001; pT181: 1.4-fold, 95% CI 1.3-1.5,P< .0001) and repetitive head impacts (Tau: 1.3-fold, 95% CI 1.2-1.4,P< .0001; pT181: 1.5-fold, 95% CI 1.4-1.7,P< .0001) in comparison to baseline. The pT181/Tau ratio was significantly higher 1 hour after the exercise and heading training, and remained elevated specifically in the heading group even after 24 hours (1.2-fold, 95% CI 1.1-1.3,P= .0024). Performance in cognitive tests revealed a significant decline in focused attention (TMT-A) and cognitive flexibility (TMT-B) after the physical exercise (TMT-A: 75.16 [95% CI, 68.3-82.01,P< .0001]; TMT-B: 80.26 [95% CI, 69.83-90.68,P< .0001]) and heading training (TMT-A: 33.76 [95% CI, 30.11-37.42,P= .0004]; TMT-B: 63.92 [95% CI, 56.99-70.84,P= .0434]). Nevertheless, the physical exercise of higher intensity without the heading had a more negative impact than heading training (TMT-A:P< .0001; TMT-B:P= .0207).CONCLUSIONS AND RELEVANCEOur study showed, that non-concussive repetitive head impacts elevate pT181-Tau and pT181/total-Tau in plasma of young adults. The increase of pT181-Tau was observed also after the intense physical activity alone, however the elevation of pT181/Tau ratio after 24 hours was highly significant and specific for non-concussive repetitive head impacts. The results support the idea that phosphorylated tau-enriched fraction of tau proteins may have long-lasting consequences in the brain of head-impacted individuals. The possible longitudinal disbalance of tau proteins induced by repetitive head impacts needs to be further investigated in larger and broader cohorts, and over longer period of time.