Rapid diagnosis of aqcuired Creutzfeldt-jakob disease with protein misfolding cyclic anplification

• Project/Area Number: 15K09307
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Takeuchi Atsuko 東北大学, 医学系研究科, 助教 (00535239)
• Co-Investigator(Renkei-kenkyūsha): Kitamoto Tetsuyuki 東北大学, 医学系研究科, 教授 (20192560)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: プリオン / クロイツフェルト・ヤコブ病 / 試験管内増幅 / 獲得型CJD / 医原性プリオン病 / PMCA / in vitro / プリオン病 / 医原性クロイツフェルトヤコブ病

Outline of Final Research Achievements

Plaque-type dura mater graft-associated Creutzfeldt-Jacob disease (p-dCJD) prions showed distinct amplification features from those of non p-dCJD (np-dCJD) prions in protein misfolding cyclic amplification (PMCA). Although no amplification from np-dCJD prions was observed with 129M or 129V substrates, p-dCJD prions were amplified drastically with the 129V substrates but not with the 129M substrates despite the PRNP codon 129 incompatibility between seed and substrate. Moreover, we found that type 2 PMCA products were newly generated from p-dCJD prions using type 2 PrPSc-specific antibody, while PrPSc in p-dCJD cases did not react with the type 2 PrPSc-specific antibody. These findings suggest that our PMCA is a useful tool for easily and rapidly identifying acquired CJD associated with the transmission of the V2 CJD strain of codon 129 methionine homozygotes, based on the preference for the 129 V substrate and the type of the amplified products.

Research Products

• [Journal Article] Application of protein misfolding cyclic amplification for the rapid diagnosis of acquired Creutzfeldt-Jakob disease. (2017)
  • Author(s): Takeuchi A, Kobayashi A, Morita M, Kitamoto T
  • Journal Title: Medical Research Archives Volume: 5
  • Peer Reviewed
• [Journal Article] Application of protein misfolding cyclic amplification for the rapid diagnosis of acquired Creutzfeldt-Jakob disease (2017)
  • Author(s): Takeuchi A, Kobayashi A, Morita M, Kitamoto T
  • Journal Title: Medical Research Archives Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt-Jakob disease in cell-protein misfolding cyclic amplification (2016)
  • Author(s): Atsuko Takeuchi, Atsushi Kobayashi, Piero Parchi, Masahito Yamada, Masanori Morita, Shusei Uno and Tetsuyuki Kitamoto
  • Journal Title: Laboratory Investigation Volume: in press Issue: 5 Pages: 581-7
  • DOI: 10.1038/labinvest.2016.27
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Diagnosis of MMiK type acquired Creutzfeldt-Jakob disease with cell- protein misfolding amplification (PMCA) (2017)
  • Author(s): Takeuchi A, Kobayashi A, Morita M, Kitamoto T
  • Organizer: 日本認知症学会
  • Int'l Joint Research / Invited
• [Presentation] Identification of the origin of Creutzfeldt-Jakob disease after cadaver-sourced pituitary growth hormone treatment using an amplification property in protein misfolding cyclic amplificatiton (2016)
  • Author(s): Takeuchi A, Yamamoto M, Parchi P, HaiK S, Morita M, Kobayashi A, Kitamoto T
  • Organizer: PRION2016
  • Place of Presentation: 学術総合センター（東京）
  • Year and Date: 2016-05-10
  • Int'l Joint Research
• [Presentation] cell-PMCA of acquired Creutzfeldt-Jakob disease (2015)
  • Author(s): Atsuko Takeuchi, Atsushi Kobayashi, Piero Parchi, Masahito Yamada, Masanori Morita, Shuusei Uno and Tetsuyuki Kitamoto
  • Organizer: Asia Pacific Society of Prion Research
  • Place of Presentation: 金沢 (石川県立音楽堂)
  • Year and Date: 2015-09-04
  • Int'l Joint Research