Dissecting mechanisms of tauopathy using multimodal imaging techniques

Abstract

Tauopathy is characterized by the fibrillar tau accumulation in central nervous system. Neurofibrillary lesions strongly correlated with cognitive deficits in neurodegenerative diseases. However, causal mechanisms of tau–induced neuronal dysfunction are still unresolved. Recent advance of in vivo imaging techniques has opened a window to capture a real time event during brain aging. Especially, researchers are going to establish positron emission tomography (PET) imaging of tau lesions using several tau PET tracers. [¹¹C]PBB3 and [¹⁸F]PM–PBB3 are promising PET tracers to diagnose not only Alzheimer's disease (AD) also non–AD tauopathies (e.g., Progressive supranuclear palsy, Corticobasal degeneration, and Chronic traumatic encephalopathy). In addition to clinical research, these PET tracers are feasible to visualize tau pathologies in mouse models of tauopathy. Therefore, tau PET imaging is a translatable research tool between human and mouse tauopathies. Furthermore, PBB3 and PM–PBB3 can be used for fluorescence imaging to detect filamentous tau inclusions in living animals using two–photon microscopy. Pathological tau–induced neurotoxicity can be examined at cellular levels in a mouse model of tauopathy. Since progression of tau pathology is closely associated with neuronal cell death, volumetric analysis by magnetic resonance imaging (MRI) is another bench mark of tau–induced neurodegeneration. At present, these multimodal imaging techniques allow verification of the pathogenesis of tauopathies. In this review, we will discuss current progress of the development of tau PET tracers and a imaging–based diagnostic platform of tauopathy.