PET Visualization of Brain Tau Accumulations Secondary to Various CNS Injuries: Chronic Traumatic Encephalopathy (CTE) and Organophosphorus Poisoning

Traumatic brain injury (TBI) can lead to severe and persistent neuropsychiatric sequelae. Recent clinical and neuropathological studies have elucidated the epidemiological link between TBI and the subsequent development of neurodegenerative diseases. Chronic traumatic encephalopathy (CTE), a neurodegenerative disorder associated with repeated mild TBI, is characterized by the deposition of hyperphosphorylated tau in neurofibrillary and astrocytic tangles, predominantly surrounding small blood vessels in the cortical sulci. Recent cryo-electron microscopy (cryo-EM) studies have shown that CTE-type tau folds appear in the brain long after the onset of some central nervous system diseases. In addition to TBI-related tauopathies, emerging evidence suggests that exposure to organophosphorus compounds, such as pesticides and nerve agents, may also contribute to long-term neuropsychiatric sequelae, including cognitive impairment and psychiatric disorders, and has been postulated to promote neuropathological changes including tau accumulation through persistent neuroinflammation and excitotoxicity. Positron emission tomography (PET) has emerged as a valuable tool for detecting molecular pathologies in neurodegenerative diseases. This review focuses on the development of tau PET tracers for in vivo visualization of tau deposition in chronic TBI states. We present current findings from tau PET imaging studies on CTE and other secondary tauopathies, utilizing both first- and second-generation tau PET tracers. Additionally, we discuss PET quantification techniques for assessing tau burden in the chronic stages of TBI, with particular emphasis on the unique topography of tau lesions in CTE.