Blood test spots brain damage from repeated head impacts in athletes
Researchers have identified a blood biomarker that can detect chronic traumatic encephalopathy in former football players exposed to repeated head trauma. The finding could transform how leagues, insurers, and medical systems screen for degenerative brain disease—potentially shifting liability and prevention strategies across professional and amateur sports.
Originaltitel: Plasma Phosphorylated Tau 217 in Participants at Risk for Chronic Traumatic Encephalopathy.
En blodtest för fosforylerat tau 217 kan identifiera hjärnskador från upprepade huvudtrauman — en upptäckt som öppnar vägen för tidig upptäckt av kronisk traumatisk encefalopati (CTE) utan att vänta på obduktion. Boston University CTE Center och Sahlgrenska University Hospital analyserade blodprover från 231 deltagare mellan 2016–2023, däribland 177 före detta amerikanska fotbollsspelare och 54 opåverkade män. Fotbollsspelarna hade högre basala p-tau217-värden (0,35 mot 0,27 pg/mL), och nivåerna steg signifikant över tid (P < 0,001). Resultatet är relevant för anhöriga och äldre som är oroliga för långtidseffekter av tidigare huvudskador eller sportkopplad exponering. Biomarkören kan framöver möjliggöra tidigare intervention och behandlingsplanering — än så länge är testet forskningsverktyg men kan påverka klinisk praktik inom fem till tio år.
IMPORTANCE: In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. OBJECTIVE: To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. EXPOSURES: RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. MAIN OUTCOMES AND MEASURES: Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [<0.40 pg/mL]), Aβ-positron emission tomography (PET; 18F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET (18F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. RESULTS: Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET-positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P < .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217-negative and Aβ-PET-positive; 7 participants were p-tau217-positive and Aβ-PET-negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.