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内容記述 |
Accumulating clinical and experimental evidence has supported the view that diverse acute neuronal insults, including traumatic brain injury (TBI), viral infections, exposure to toxic substances, and lobectomy, induce functional and neuropathological alterations later in life, which are distinct from early-stage injuries. The late-stage neurodegenerative processes in a subset of these conditions are characterized by protein deposits composed of hyperphosphorylated tau, which is also a neuropathological hallmark of aging-related neurodegenerative disorders exemplified by Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) disorders. A typical delayed-onset condition caused by mild-repetitive TBI is chronic traumatic encephalopathy (CTE),1 formerly known as boxer’s encephalopathy. CTE is characterized by the deposition of hyperphosphorylated tau protein as neurofibrillary tangles around small blood vessels of the cortex, typically at the sulcal depths. Recent cryo-EM studies have revealed that the three-dimensional structure of tau folds in CTE differs from those of other tauopathies2. Interestingly, accumulation of CTE-type tau fold has been observed not only in mild-repetitive TBI but also in different types of brain damage, such as chronic viral infections,3 indicating that TBI and other brain damage share a common pathology that causes late-stage tau accumulation. The positron emission tomography (PET) imaging technology has enabled visualization of these protein accumulations in the brains of living subjects.4 We have reported that PET scanning with first-generation tau tracer 11C-PBB3 can detect tau depositions in the brain of patients with a history of various types ofTBI.5 The second-generation tau tracer, 18F-florzolotau (18F-APN-1607/18F-PM-PBB3), has been indicated to enable the diagnosis of a wide-range of tauopathies at the single-case level 4. In this presentation, we will report the results of our ongoing tau PET study of former professional boxers (N=29, 43.4 ± 10.3 years old). Our results showed that boxers had increased accumulation of 18F-florzolotau in multiple brain regions compared to age-matched healthy control subjects (N=27), and that increased accumulation of 18F-florzolotau is associated with increased plasma GFAP levels. A significant correlation between SUVR values in the whole gray matter and the total number of professional bouts indicates the cumulative effects of concussion on tau accumulation. Subtyping using z-score heatmap with predetermined criteria revealed heterogeneity in 18F-florzolotau retention patterns in boxers, and each type varies in longitudinal changes of 18F-florzolotau retention patterns, as well as in clinical features. These results suggest that PET scanning with 18F-florzolotau is useful for evaluating tau pathology following mild-repetitive TBI at the single-case level. We also show a 25-year clinical observation of the case of severe sarin poisoning in the Tokyo subway sarin attack. Longitudinal structural MRI and SPECT evaluation showed progressively enlarging areas of cerebral atrophy and reduced cerebral blood flow, suggesting long-lasting neuronal damage in sarin-affected brain regions. Furthermore, late-stage neuropathological sequelae of sarin exposure were visualized by the accumulation of tau PET tracer coinciding with areas of brain atrophy and prominent elevations in plasma GFAP levels. |
