An Investigation on Repetitive Head Impact Exposure and Plasma Total Tau Concentrations in Former National Football League Players (S7.004)

Objective: To determine the potential of plasma total tau (t-tau) as a screening biomarker for chronic traumatic encephalopathy (CTE). Background: CTE is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. The lack of validated biomarkers precludes in vivo diagnosis of CTE. Blood protein analysis of t-tau has diagnostic utility in Alzheimer’s disease, and RHI correlates with acute plasma t-tau elevations. Plasma t-tau may detect long-term neurological conditions from RHI, including CTE, and we examined this possibility using a sample of symptomatic former NFL players presumably at high risk for CTE. Design/Methods: 96 symptomatic former NFL players (ages 40–69) and 25 same-age controls underwent blood draw and completed neuropsychological and neuropsychiatric testing. Quanterix Simoa-HD1 tau assay measured plasma t-tau, and Principal Component Analysis derived clinical function composites. The cumulative head impact index (CHII) estimated RHI exposure. Analysis of variance adjusting for age examined between group differences in plasma t-tau. Receiver operating characteristic curve identified the plasma t-tau concentration with 100% specificity to former NFL players. Partial correlations controlling for age and body mass index examined associations between plasma t-tau with the CHII and clinical function. Results: A higher CHII predicted greater plasma t-tau in the former NFL players (p=0.0137). There were no group differences, but former NFL players tended to have plasma t-tau values in the higher end of the range (p=0.04). Plasma t-tau of 3.56 pg/mL was 100% specific to 12 former NFL players; no controls had concentrations at this level. Former NFL players with plasma t-tau ≥3.56 had a higher CHII versus the remaining sample (p=0.018). Plasma t-tau did not predict clinical function (p>0.05). Conclusions: Greater RHI exposure predicted higher later-life plasma t-tau. Because plasma t-tau is inexpensive and non-invasive, further study on it as a screening biomarker for CTE is warranted, including repeating this study once CTE can be clinically diagnosed. Study Supported by: This work was supported by grants from the National Institutes of Health (NIH; R01 NS 078337; R56 9500304025; U01 NS093334). This publication was also supported by the National Center for Advancing Translational Sciences, NIH, through BU-CTSI Grant Number 1UL1TR001430. Michael L. Alosco and research reported in this publication is supported by the NIH under grant number 1F32NS096803-01. Christine Baugh is currently supported by the National Institutes of Mental Health under award number T32MH019733. The plasma total tau assays were performed at Quanterix (Lexington, MA) at no cost. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. There is no sponsor. Disclosure: Dr. Alosco has nothing to disclose. Dr. Tripodis has nothing to disclose. Dr. Jarnagin has nothing to disclose. Dr. Baugh has received research support from the National Collegiate Athletic Association and the National Football League Players9 Association. Dr. Martin has nothing to disclose. Dr. Chaisson has nothing to disclose. Dr. Estochen has received personal compensation for activities with Quanterix as an employee. Dr. Song has received personal compensation for activities with Quanterix as an employee. Dr. Cantu has nothing to disclose. Dr. Jeromin has received personal compensation for activities with Quanterix Corporation as an employee. Dr. Jeromin has received compensation for serving as an advisor of Quanterix Corporation. Dr. Jeromin holds stock and/or stock options in Quanterix Corporation, which sponsored research in which Dr. Jeromin was involved as an investigator. Dr. Jeromin holds stock and/or stock options in Quanterix Corporation. Dr. Stern has received personal compensation for activities with Biogen, Avanir Pharmaceuticals, the NCAA, and Eli Lilly. Dr. Stern has received royalty payments from Psychological Assessment Resources, Inc. Dr. Stern has received research support from Avid Radiopharmaceuticals, Amarantus, Eisai, and Eli Lilly.