PET Imaging of Neurodegeneration With [18F]AV-1451 PET After Repetitive Traumatic Brain Injury

Abstract

INTRODUCTION TBI (traumatic brain injury) is associated with an increased risk of late neurodegeneration in chronic TBI survivors. The underlying pathophysiology of trauma-related neurodegeneration is hypothesized to involve a tauopathy, with p-tau deposited in beta-pleated sheets. Current research focuses on identifying strategies to detect trauma-related neurodegeneration in-Vivo. [F-18]AV-1451, a tau-specific PET radiotracer, may detect hyper-phosphorylated tau deposits in living patients. METHODS Participants with a history of TBI >6 mo prior with concern for cognitive decline with age-matched controls were recruited. Subjects were classified into three groups: few (=3 TBI exposures), intermediate (4–10 exposures), and numerous (>10 exposures). Participants underwent PET imaging with [F-18]AV-1451, and qualitative and semi-quantitative (SUVR) analyses of radiotracer retention were performed. Visual classification of tau positivity (+/−) was performed with absence of established positivity thresholds for [F-18]AV-1451 SUVR values. All subjects underwent neuropsychological evaluation, including measures of processing speed, executive function, and memory. RESULTS Twenty-seven TBI subjects and 7 controls were enrolled. A total of 9 participants were categorized as few, 2 as intermediate, 7 as numerous. All TBI subjects demonstrated impairment on at least one neurocognitive measure, while control subjects had normal neuropsychological test results. Analysis of [F-18]AV-1451 uptake patterns demonstrated evidence of tauopathy in 3 subjects, based on visual reads. Significantly increased [F-18]AV-1451 retention was noted in occipital gray matter, posterior cingulate gyrus, and parietal cortex in these 3 tau (+) TBI subjects compared to 24 TBI subjects visually classified as tau (−) and also normal controls. CONCLUSION Evidence of tauopathy, indicative of trauma-related neurodegeneration, was noted in 3 chronic TBI subjects, all of whom were categorized as numerous (>10) TBI exposures and cognitive deficits on neuropsychological testing. No tau PET [F-18]AV-1451 uptake was noted in control participants or in participants categorized as few or intermediate. The data represent a possible [F-18]AV-1451 PET uptake pattern associated with a clinical neurodegeneration syndrome in repetitive TBI.