Neuropathological studies of thalamic form of Creutzfeldt-Jakob disease using protein misfolding cyclic amplification
| Project/Area Number |
18K07490
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | プリオン病 / クロイツフェルト・ヤコブ病 / PMCA法 / プリオン / クロイツフェルトヤコブ病 / 視床型プリオン病 / in vitro / 試験管内増幅 / 視床型クロイツフェルト・ヤコブ病 / 致死性家族性不眠症 / in vitro増幅法 |
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| Outline of Final Research Achievements |
Fatal familial insomnia (FFI) is a genetic prion disease which is associated with the D178N point mutation at the prion protein (PrP) gene. Although the hallmark pathologic feature is thalamic and olivary degeneration, there is an atypical FFI patient without the hallmark feature. We compared one atypical clinicopathologic FFI phenotype case and typical FFI phenotype cases or sporadic fatal insomnia (sFI) cases with protein misfolding cyclic amplification (PMCA). PMCA could amplify both typical FFI cases and sFI cases but not the atypical FFI phenotype or other sporadic Creutzfeldt-jakob disease subtypes. In addition to clinical findings and neuropathological features, the transmission properties using humanized knock-in mice and the amplification properties were also different between the typical and the atypical FFI phenotyps. It is suggested that two distinct prions were associated with the diversity in the FFI phenotype.
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| Academic Significance and Societal Importance of the Research Achievements |
PMCA法はCJDの発症前診断やプリオンの高感度検出系として期待されてきた。しかしながらヒトプリオンへの応用は今日まで困難であり、増幅に成功したのはこれまで変異型CJDのみであったが、本研究ではsCJD-MM2Tを引き起こすM2TプリオンのPMCA法による高感度検出を成功させた。免疫染色やウェスタンブロット法でも検出量は極めて微量、実験動物への感染もほぼ成立しないこのM2Tプリオンの高感度検出法が確立したことにより、その脳内での局在性や視床型プリオン病の鑑別診断にも応用可能となった。
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Report
(4 results)
Research Products
(3 results)
