Development of diagnostic and therapeutic agents targeting pre- fibrillary tau lesions in Tauopathies.

• Project/Area Number: 21791158
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: MARUYAMA Masahiro National Institute of Radiological Sciences, 分子イメージング研究センター, 主任研究員 (80396481)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: タウオパチー / ポジトロン断層撮影 / 未線維タウ構造体 / ビトロネクチン / 線維性封入体形成機構 / 未線維化タウ病変 / イメージング

Research Abstract

A series of newly developed tau imaging probes applicable to positron emission tomography (PET) exhibited pharmacological properties sufficient for quantitative detection of intraneuronal tau inclusions (TI) formed in tau transgenic mice (tau-Tg). Combined PET and postmortem neuropathological assays of aged tau-Tg indicated that relatively immature tau assemblies in the hippocampus led neurons to toxic death prior to the formation of TI, while abundant accumulation of TI appeared to be associated with gradual neuronal death in the brainstem and spinal cord. This regional difference may be mechanistically linked to interaction of bioactive molecules with tau aggregates, as an adhesion element, vitronectin (Vn), was well colocalized with neuronal tau in the brainstem but not hippocampus. In this consideration, Vn is likely to be involved in conversion of tau polymers between immature neurotoxic and mature nontoxic forms, which would provide insights into etiological and diagnostic-therapeutic approaches to low-order tau assemblies.

Research Products

• [Journal Article] In-vivo visualization of key molecular processes involved in Alzheimer's disease pathogenesis : Insights from neuroimaging research in humans and rodent models. (2010)
  • Author(s): Higuchi M, Maeda J, Ji B, Maruyama M, Okauchi T, Tokunaga M, Ono M, Suhara T.
  • Journal Title: Biochim Biophys Acta. 1802 Pages: 373-388
  • Peer Reviewed
• [Journal Article] In-vivo visualization of key molecular processes involved in Alzheimer's disease pathogenesis : Insights from neuroimaging research in humans and rodent models. (2010)
  • Author(s): Higuchi M, Maeda J, Ji B, Maruyama M, Okauchi T, Tokunaga M, Ono M, Suhara T.
  • Journal Title: Biochim Biophys Acta. Volume: 1802 Pages: 373-88
  • Peer Reviewed
• [Presentation] タウ封入体を標的としたタウオパチー診断薬の開発 (2009)
  • Author(s): 丸山将浩
  • Organizer: 第28回日本認知症学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2009-11-20
• [Presentation] タウ封入体を標的としたタウオパチー診断薬の開発 (2009)
  • Author(s): 丸山将浩
  • Organizer: 第28回日本認知症学会学術集会
  • Place of Presentation: 東北大学,仙台
  • Year and Date: 2009-11-20
• [Presentation] In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies. (2009)
  • Author(s): Maruyama M, et al.
  • Organizer: Alzheimer's Association ICAD 2009.
  • Place of Presentation: Vienna.
  • Year and Date: 2009-07-11
• [Presentation] In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies (2009)
  • Author(s): Masahiro Maruyama
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease 2009
  • Place of Presentation: Venna, Austria
  • Year and Date: 2009-07-11