National Institute of Radiological Sciences, Japan
Title: Tau PET imaging: New insight into early diagnosis of tauopathy
Naruhiko Sahara received his BS from the Tokyo University of Science, Canada in 1988. MS from Tokyo University of Science in 1990 in the Department of Biochemistry and PhD from Tokyo University of Science in the Department of Biochemistry in 1998. From 1992-1998, he worked as a Research Technologist in the Department of Molecular Biology in Tokyo Institute of Psychiatry, Tokyo, Japan. 1998-2000 as a Research associate in Department of Neuroscience, Osaka City University, Japan. 2000-2003 Research fellow in Laboratory of Neurochemistry, Mayo Clinic, Jacksonville. From 2003-2006, he worked as a Staff Scientist in Laboratory for Alzheimer’s Disease, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN) in Japan. 2006-2008 he was Deputy Laboratory Head in Laboratory for Alzheimer’s Disease, Brain Scinence Institute, RIKEN in Japan. From 2008-2009, Senior Research Associate, Laboratory of Neurodegenerative Disease Modeling, Mayo Clinic. 2009-2010, he worked as an Associate Consultant in Laboratory of Neurodegenerative Disease Modeling in Mayo Clinic, Jacksonville. 2010-2013 as Assistant Professor in Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville. 2013-present he is working as a Senior Researcher and Assistant Director, Neuromolecular Dynamics Team in Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Accumulation of intracellular neurofibrillary tangles (NFTs) consisting of microtubule-associated protein tau is a major hallmark of Alzheimer’s disease (AD) and related neurodegenerative diseases regarded as ‘tauopathies’. Findings of tau gene mutations in FTDP-17-taufamilies have provided direct evidence that tau abnormalities alone can induce neurodegenerative disorders. Therefore, visualization of tau accumulation would offer a reliable, objective indicator to diagnose of tauopathy and to assess the disease progression. Positron emission tomography (PET) imaging of tau lesions is currently available using several tau PET ligands including [11C]PBB3. However, more compelling in vivo and neuropathological evidence supporting binding of PBB3 to tau lesions in diverse tauopathies(e.g., AD, Progressive supranuclear palsy, Corticobasal degeneration, Argyrophilic grain disease, Pick’s disease) is still requiredsince the presence of tau pathologies in scanned subjects has not been confirmed in the aforementioned clinical PET assay. PBB3 is a fluorescent compound, and is accordingly supposed to be useful for multimodal imaging studies, potentially allowing us to validate its binding to diverse tau inclusions (e.g., NFTs, globus NFTs, astrocytic plaques, tufted astrocytes, coiled bodies, Pick bodies, and ballooned neurons) by histological methods.Here, I will present our progress of pathological characteristics of PBB3 binding on tau lesions in brains of human subjects with various tauopathies and tau transgenic mice. Moreover, ongoing studies will be introduced for the usefulness of tau PET ligands in the early detection of tauopathies.