Investigating the Use of [18-F] tau-PET Imaging as a Biomarker of tau Pathology in Retired Athletes at Risk of Neurodegeneration
The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer’s disease and chronic traumatic encephalopathy. Chronic traumatic encephalopathy is characterized by abnormal accumulation of tau protein in the brains of affected athletes in a pattern distinct from other neurodegenerative diseases. There is currently no in vivo biomarker of tau pathology of chronic traumatic encephalopathy, and the diagnosis is made post-mortem. [18-F] Flortaucipir tau-PET has shown high specificity to tau pathology of Alzheimer’s disease, but studies in chronic traumatic encephalopathy are inconclusive. This study investigated the use of flortaucipir tau-PET in a cohort of former athletes negative for Alzheimer’s disease biomarkers. We first investigated the relationship between genetic risk factors and tau-PET as an indirect measure of tau pathology. We found an association between higher cortical grey matter tau burden as seen with flortaucipir and the APOE4 allele in former athletes. APOE4 allele may be a risk factor for tau accumulation in former contact sports athletes at high risk of neurodegeneration. Next, we investigated the use of phosphorylated tau at threonine 181 (p-tau181) in plasma as an additional biomarker of tau pathology. Although high plasma p-tau181 levels were associated with brain abnormalities, baseline p-tau181 did not predict longitudinal changes in regional brain volumes or white matter integrity in athletes and was at normal levels in a neuropathologically confirmed chronic traumatic encephalopathy case. Plasma p-tau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression. Due to plasma p-tau181 specificity to Alzheimer’s disease pathology, we therefore used it as an additional accessible biomarker to control for presence of Alzheimer’s disease in our cohort. Lastly, we assessed the association of flortaucipir tau-PET with brain volumes in retired athletes; and examined the relationship between tau-PET and neuropsychological functioning. A higher tau-PET signal was associated with reduced grey matter volumes and lower memory scores. Overall, our results show that flortaucipir tau-PET may be useful for identifying neurodegenerative changes in former athletes negative for Alzheimer’s disease pathology. Future neuropathological studies can examine the specificity of flortaucipir to tau pathology of chronic traumatic encephalopathy.
athletes, concussion, imaging, neurodegeneration, PET, tau
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