Association of prion proteins with other neurodegenerative disease-related proteins

• Project/Area Number: 18K06506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: National Center of Neurology and Psychiatry (2020-2022); Saitama Medical University (2018-2019)
• Principal Investigator: Takao Masaki 国立研究開発法人国立精神・神経医療研究センター, 病院 臨床検査部, 部長 (50245487)
• Co-Investigator(Kenkyū-buntansha): 美原 盤 公益財団法人脳血管研究所, その他部局等, 研究員(移行) (30190721)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: プリオン / クロイツフェルト・ヤコブ病 / アミロイドベータ / タウ / アルツハイマー病 / プリオン病 / アミロイド / 神経病理 / 網膜 / アミロイドβ / αシヌクレイン / TDP-43

Outline of Final Research Achievements

Fifty one CJD cases were studied. Mean age was 71±11 ys. Thal phase (amyloid beta) was 0 (29 cases), 1-2 (15 cases), 3 (3 cases), and 4-5 (4 cases). Braak stage of progression of tau protein was 0 (17), 1-2 (28), 3-4 (5), and 5-6 (1). ADNC was none (30), low (16), intermediate (5), high (0). The results showed a significant difference in tau between SCJD and FCJD, with the SCJD group having a significantly milder tau level. The possibility of an association between prion protein deposition and neurodegenerative disease-related proteins in some cases cannot be ruled out and requires further investigation.

Academic Significance and Societal Importance of the Research Achievements

プリオン病はBSEによって種の壁を越える伝達性疾患である。近年アルツハイマー病のアミロイドβ、タウ、パーキンソン病におけるαシヌクレインなどもプリオンと同様な機序で脳内を伝達拡大することや、一部の状況下では他人の組織から感染する可能性（屍体から採取して使用した硬膜）も指摘されており、プリオン病の病態を解明することは重要である。本研究で得られた成果がただちにプリオン病の病態解明に繋がるものではないものの、近年のCryo-EMにより、神経変性疾患関連蛋白の原子構造が次々と明らかになり、今後、原子構造からみた研究によっても、プリオンやほかの神経変性疾患関連蛋白との関連なども明らかになる可能性がある。

Research Products

• [Journal Article] An autopsy case of progressive multifocal leukoencephalopathy with massive iron deposition in juxtacortical lesions (2023)
  • Author(s): Okamoto Kosuke、Takeda Akitoshi、Hatsuta Hiroyuki、Sano Terunori、Takao Masaki、Ohsawa Masahiko、Miki Yukio、Nakamichi Kazuo、Itoh Yoshiaki
  • Journal Title: Neuropathology Volume: Online ahead of print Issue: 5 Pages: 396-402
  • DOI: 10.1111/neup.12898
  • Peer Reviewed / Open Access
• [Journal Article] Neuropathology for neuropsychologists (2022)
  • Author(s): 高尾 昌樹
  • Journal Title: Japanese Journal of Neuropsychology Volume: 38 Issue: 2 Pages: 80-85
  • DOI: 10.20584/neuropsychology.17144
  • ISSN: 0911-1085, 2189-9401
  • Year and Date: 2022-06-25
  • Peer Reviewed
• [Journal Article] Age-dependent formation of TMEM106B amyloid filaments in human brains (2022)
  • Author(s): Schweighauser M, Arseni D, Bacioglu M,.... Takao M,......, Goedert M, Scheres SHW.
  • Journal Title: Nature Volume: - Issue: 7909 Pages: 310-314
  • DOI: 10.1038/s41586-022-04650-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neurological post‐acute sequelae of <scp>SARS‐CoV</scp> ‐2 infection (2022)
  • Author(s): Takao Masaki、Ohira Masayuki
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 77 Issue: 2 Pages: 72-83
  • DOI: 10.1111/pcn.13481
  • Peer Reviewed / Open Access
• [Journal Article] 【プリオン病】プリオン病の自然歴調査 JACOPの進捗 (2022)
  • Author(s): 塚本 忠, 雑賀 玲子, 高尾 昌樹, 水澤 英洋
  • Journal Title: 脳神経内科 Volume: 97 Pages: 418-423
• [Journal Article] Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt?Jakob disease patients (2021)
  • Author(s): Dong Thi-Thu-Trang、Akagi Akio、Nonaka Toshiaki、Nakagaki Takehiro、Mihara Ban、Takao Masaki、Iwasaki Yasushi、Nishida Noriyuki、Satoh Katsuya
  • Journal Title: Neurobiology of Disease Volume: 159 Pages: 105504-105504
  • DOI: 10.1016/j.nbd.2021.105504
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type (2020)
  • Author(s): Hamaguchi T, Sanjo N, Ae R, Nakamura Y, Sakai K, Takao M, Murayama S, Iwasaki Y, Satoh K, Murai H, Harada M, Tsukamoto T, Mizusawa H, Yamada M.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 91 Issue: 11 Pages: 1158-1165
  • DOI: 10.1136/jnnp-2020-323231
  • Peer Reviewed / Open Access
• [Journal Article] Importance of Neuropathological Diagnosis of Dementia Patients in Family Practice (2019)
  • Author(s): Tanaka Y, Ikeda M, Mihara B, Ikeda Y, Sato K, Kitamoto T, Takao M.
  • Journal Title: JMA Journal Volume: 2 Issue: 2 Pages: 148-154
  • DOI: 10.31662/jmaj.2018-0060
  • NAID: 130007713783
  • ISSN: 2433-328X, 2433-3298
  • Year and Date: 2019-09-04
  • Peer Reviewed / Open Access
• [Journal Article] A novel combination of prion strain co-occurrence in patients with sporadic Creutzfeldt-Jakob disease (2019)
  • Author(s): Kobayashi Atsushi、Iwasaki Yasushi、Takao Masaki、Saito Yuko、Iwaki Toru、Qi Zechen、Torimoto Ryouta、Shimazaki Taishi、Munesue Yoshiko、Isoda Norikazu、Sawa Hirofumi、Aoshima Keisuke、Kimura Takashi、Kondo Hinako、Mohri Shirou、Kitamoto Tetsuyuki
  • Journal Title: The American Journal of Pathology Volume: 印刷中 Issue: 6 Pages: 1276-1283
  • DOI: 10.1016/j.ajpath.2019.02.012
  • NAID: 120006847766
  • Peer Reviewed
• [Journal Article] PrPres deposition in the retina is a common finding of sporadic, familial and iatrogenic Creutzfeldt-Jakob diseases (CJD) (2018)
  • Author(s): Takao M, Kimura H, Kitamoto T, Mihara B.
  • Journal Title: Acta Neuropathol Commun. Volume: 6 Issue: 1 Pages: 78-78
  • DOI: 10.1186/s40478-018-0582-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] V180I変異を有する家族性CJD 103歳の剖検例 (2022)
  • Author(s): 針谷 康夫, 金井 光康, 田野 光敏, 北本 哲之, 高尾 昌樹, 美原 盤
  • Organizer: 第41回日本認知症学会学術集会 第37回日本老年精神医学会 合同開催
• [Presentation] V180I変異による遺伝性クロイツフェルト・ヤコブ病の自然歴 (2022)
  • Author(s): 雑賀 玲子, 塚本 忠, 高尾 昌樹, 山田 正仁, 阿江 竜介, 濱口 毅, 三條 伸夫, 北本 哲之, 佐藤 克也, 桑田 一夫, 水澤 英洋
  • Organizer: 第41回日本認知症学会学術集会 第37回日本老年精神医学会 合同開催
• [Presentation] Establishment of brain bank for human prion diseases (2020)
  • Author(s): Takao M, Tano M, Inoue T, Shirayoshi T, Kanai M, Furui K, Mihara B.
  • Organizer: The 96th Annual Meeting, Virtual meeting
  • Int'l Joint Research
• [Presentation] Prion disease associated with a novel 96bp insertional mutation in the octapeptide repeat region. (2019)
  • Author(s): Takao M, Honda K, Koide M, Arai K,Mihara B, Kitamoto T.
  • Organizer: American Association of Neuropathologists, Inc. The 95th Annual Meeting
  • Int'l Joint Research
• [Presentation] PrPres deposition in the retina of sporadic, familial and iatrogenic Creutzfeldt-Jakob diseases (CJD) (2018)
  • Author(s): Takao M, Kimura H, Kitamoto T, Mihara B.
  • Organizer: 19th International Congress of Neuropathology (ICN)
  • Int'l Joint Research