Neuropathological studies of thalamic form of Creutzfeldt-Jakob disease using protein misfolding cyclic amplification

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tohoku University
• Principal Investigator: Takeuchi Atsuko 東北大学, 医学系研究科, 助教 (00535239)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: プリオン病 / クロイツフェルト・ヤコブ病 / PMCA法

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.

Free Research Field

プリオン病

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。