Amateur Soccer Heading and Acute Elevations in Blood-Based p-Tau217 and S100B

Importance Former professional soccer players have increased risk of neurodegenerative disease, potentially due to cumulative exposure to repetitive head impacts such as heading. However, the acute effects of heading on neural integrity remain unclear. Objective To assess the acute association of real-life heading with blood biomarkers of neural damage before and after soccer matches. Design, Setting, and Participants In this prospective population-based case-control study, soccer players participated in organized matches (August-December 2024). Blood samples were collected prematch and immediately and delayed postmatch (<1 and 24-48 hours, respectively). Video analysis quantified heading exposure, including frequency and intensity. Exercise intensity was monitored using local position monitoring and heart rate analysis. Players from higher-level amateur soccer competitions were recruited through communication channels of the Royal Dutch Football Association and screened for eligibility. Inclusion criteria included the following: male sex, age older than 18 years, and no history of a neurological condition. Exposure Real-life heading exposure during a single amateur soccer match. Main Outcomes and Measures Blood biomarkers of neural damage were measured and included the following: phosphorylated tau 217 (p-tau217), brain-derived tau (BD-tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), S100B calcium-binding protein (S100B), and neuron-specific enolase (NSE). The main outcome was the association between heading exposure and change in biomarker concentration, assessed with linear mixed models while correcting for exercise intensity. Results A total of 389 soccer players were screened for eligibility. Among the 302 players participating in 1 of the 11 matches (mean [SD] age, 24.6 [5.2] years), 216 (72%) had heading exposure. Mean (SD) exposure was 2.0 (2.1) headers per player per match, and 48% of players had high-impact heading exposure (ball trajectories >20 m; 80 players [26%] with exposure to a single high-impact header; 65 players [22%] with exposure to multiple high-impact headers). Players exposed to heading showed significantly greater immediate postmatch increases in S100B concentration (n = 299, P = .03; Cohen d = 0.29) compared with unexposed players. Exposure to more headers was associated with greater increases in S100B (n = 299, P = .02; Cohen d = 0.07 per header) and p-tau217 concentration (n = 296, P = .01; Cohen d = 0.09 per header). High-impact headers were also associated with greater increases in p-tau217 (n = 148, P = .03; Cohen d = 0.40) and S100B concentration (n = 149, P = .02; Cohen d = 0.43) compared with no exposure. Observed biomarker elevations normalized within 24 to 48 hours. No other significant associations were found. Results were robust to sensitivity analysis adjusting for blood volume. Conclusion and Relevance Findings of this case-control study show that soccer heading was associated with acute increases in blood biomarkers of neural damage, including dose-response relationships. These findings suggest that amateur-level heading may acutely affect neural integrity.