2010 Fiscal Year Final Research Report
Development of diagnostic and therapeutic agents targeting pre- fibrillary tau lesions in Tauopathies.
| Project/Area Number |
21791158
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | National Institute of Radiological Sciences |
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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)
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| Project Period (FY) |
2009 – 2010
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| 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 |
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| 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.
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