[Chiba Medical Society Award Review] Tau PET imaging study to elucidate the pathogenesis of neurodegenerative disorders and facilitate drug discovery process

[ABSTRACT]Abnormal proteins deposited in the brain exemplified by amyloid-beta and tau lesions are pathognomonic hallmarks of neurodegenerative disorders. Increasing evidence suggests that these abnormal proteins have pivotal roles in the disruption of the brain environment, leading to the onset of neurodegenerative diseases. The resulting accumulation of abnormal proteins in the brain is considered to represent important target molecules for both diagnostic and therapeutic purposes. In recent years, the development of PET imaging technology for visualizing abnormal brain proteins has been remarkable. Amyloid PET is a most successful imaging technique, and the technology has already matured sufficiently to a practical level to become an indispensable technology in the fields of dementia research and drug discovery. Following amyloid PET, tau PET was developed as a practical pathological imaging technique. Partly because tau lesions are thought to be more closely related to neurological deficits than amyloid-beta deposition, and partly because they are observed in many dementias other than Alzheimer's disease, they are expected to be a game changer in dementia research and drug discovery. In this review, I will focus mainly on tau PET imaging, and especially with PBB3 and PM-PBB3, which were originally developed by our institute, and introduce the current status of their technology development, the characteristics of each tau PET ligand, and the latest findings from clinical PET research. Furthermore, the role and future potential of neuropathological imaging in clinical research and drug discovery for dementia will be discussed.