並列タイトル等ホルマリンRT-QuIC法は孤発性クロイツフェルト・ヤコブ病患者のホルマリン固定後脳からプリオンシード活性を検出できる
授与機関名Nagasaki University (長崎大学)
一般注記Background: The neuropathology of sporadic Creutzfeldt–Jakob disease (sCJD) is usually investigated using formalin-fixed and formic acid-treated brain tissue. However, formalin and formic acid treatment can interfere with immunostaining of abnormal prion protein. Therefore, there is a need for biochemical methods other than immunostaining to investigate abnormal prion protein in postmortem tissue. We developed RT-QuIC to quantitate the seeding activity (SD50) of sCJD brain tissue treated with formalin and formic acid.Methods: We used endpoint RT-QuIC assays to analyze SD50 in formalin-fixed brain tissue from 19 sCJD patients (14 MM1 cases, 3 MM2-thalamic form [MM2T] cases and 2 MM2-cortical form [MM2C] cases) diagnosed according to Parchi's classification. We assessed SD50 in brains after incubation in formalin solution for over 1 month, and after treating formalin-fixed brain tissue with formic acid. We also examined how the SD50 values from formalin-fixed brain samples compared with neuropathological and immunohistochemical findings.Results: The SD50 values of formalin-fixed brain samples from 14 MM1 cases, 2 MM2C cases, and 2 MM2T cases were 107.77±0.57/g tissue, 107.44±0.24/g tissue and 106.00±0.77/g tissue, respectively. The average SD50 value in MM1 unfixed brains decreased by 102.04 after formalin fixation for 1 month. In MM1 cases, after combined formalin and formic acid treatment, the SD50 value was reduced by approximately 105.16 compared with that of unfixed tissue. The SD50 values of formalin-fixed tissue showed a consistent pattern with the neuropathological findings in most brain regions examined.Conclusion: RT-QuIC enables the study of formalin-fixed brain tissue from sCJD patients that has not previously been amenable to analysis.
博(医歯薬)甲第1468号 学位授与年月日:令和4年9月16日
Author: Thi-Thu-Trang Dong, Akio Akagi, Toshiaki Nonaka, Takehiro Nakagaki, Ban Mihara, Masaki Takao, Yasushi Iwasaki, Noriyuki Nishida, Katsuya Satoh
Citation: Neurobiology of Disease, 159, art.no. 105504; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2022-09-16)
著作権情報© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
関連情報http://hdl.handle.net/10069/00041834
関連情報(DOI)10.1016/j.nbd.2021.105504
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)