Examination of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in former elite American football players

Abstract INTRODUCTION Blood‐based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players. METHODS The sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45–74). Plasma assays were conducted for beta‐amyloid (Aβ) 40, Aβ42, hyper‐phosphorylated tau (p‐tau) 181+231, total tau (t‐tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin‐6 (IL‐6), Aβ42/p‐tau181 and Aβ42/Aβ40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES). RESULTS P‐tau181 and p‐tau231(p adj = 0.016) were higher and Aβ42/p‐tau181 was lower(p adj = 0.004) in football players compared to controls. Discrimination accuracy for p‐tau was modest (area under the curve AUC = 0.742). Effects were not attributable to AD‐related pathology. Younger age of first exposure (AFE) correlated with higher NfL (p adj = 0.03) and GFAP (p adj = 0.033). Plasma GFAP was higher in TES‐chronic traumatic encephalopathy (TES‐CTE) Possible/Probable (p adj = 0.008). DISCUSSION Plasma p‐tau181 and p‐tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI‐related neuropathologies. Highlights Former football players had higher plasma p‐tau181 and p‐tau231 and lower Aβ42/ptau‐181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES‐CTE possible/probable compared to TES‐CTE no/suggestive.