Development of ligands for early diagnosis and mechanistic controls of tauopathies

2015 Fiscal Year Final Research Report

• Project/Area Number: 23390235
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: Higuchi Makoto 国立研究開発法人放射線医学総合研究所, 分子イメージング研究センター, チームリーダー (10373359)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 神経科学 / 生体分子 / 認知症 / 脳疾患研究 / 薬学 / イメージング

Outline of Final Research Achievements

This project was aimed at developing potential diagnostic and therapeutic ligands for tau aggregates and other key molecules mechanistically implicated in the pathogenesis of Alzheimer’s disease and allied tauopathies. A novel radioligand, [11C]PBB3, was generated and applied to positron emission tomography (PET) of model mice and humans, providing the first demonstration of visualization of diverse tau lesions in living brains. 18F-labeled PBB3 derivatives were also produced for wider availability, and were assessed by animal PET. PET probes for deleterious microgliosis and enzymes responsible for potentiation of proinflammatory chemokines were also developed, and enabled in vivo monitoring of crosstalk between tau pathologies and neuroinflammation. A subset of PBB3 analogs was shown to suppress self-assembly of tau, indicating the capability of these chemicals as therapeutic agents.

Free Research Field

神経科学