Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt-Jakob disease patients

• Material Type: 博士論文
• Title: Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt-Jakob disease patients
• Author/Editor: DONG, THI THU TRANG
• Author Heading: DONG, THI THU TRANG
• Publication, Distribution, etc.: Elsevier Inc.
• Publication Date: 2022-09-16
• Publication Date (W3CDTF): 2022-09-16
• Alternative Title: 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
• Periodical title: Neurobiology of Disease
• No. or year of volume/issue: 159
• Volume: 159
• Pages: 105504-
• ISSN (Periodical Title): ISSN : 0969-9961
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2022-09-16
• Dissertation Number: 甲医歯薬第1468号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: RT-QUIC assay; Prion; Prion-seeding activity; Neuropathology
• Target Audience: 一般
• Note (General): 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)
• Source: https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27743&item_no=1&attribute_id=70&file_no=1 （fulltext）; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27743&item_no=1&attribute_id=70&file_no=1
• Access Restrictions: インターネット公開
• Rights (production): © 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/).
• Related Material: http://hdl.handle.net/10069/00041834
• Related Material (DOI): 10.1016/j.nbd.2021.105504
• Data Provider (Database): 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）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ