• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

New blood biomarker for Kii ALS/PDC

Research Project

Project/Area Number 18K07368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionMie University

Principal Investigator

KOKUBO Yasumasa  三重大学, 地域イノベーション学研究科, 招へい教授 (60263000)

Co-Investigator(Kenkyū-buntansha) 森本 悟  三重大学, 医学系研究科, リサーチアソシエイト (00816952)
葛原 茂樹  鈴鹿医療科学大学, 看護学部, 教授 (70111383)
Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords筋萎縮性側索硬化症 / パーキンソン認知症複合 / 血液バイオマーカー / SIMOA / PET / タウ / アミロイドβ / PET タウ / パーキンソン症候群 / 認知症 / Immunomagnetic Reduction / ALS / PDC / プロテイノパチー
Outline of Final Research Achievements

In this study, the highly sensitive ELIZA method SIMOA (Single Molecular Assay) was used to develop a useful and simple blood biomarker for the diagnosis of Kii ALS/PDC. Samples were collected and analyzed from 11 patients, including three who underwent tau PET analysis. Among these, an autopsy case in which both SIMOA and tau PET analysis were performed was obtained, and a comparative analysis of brain pathology and imaging and blood biomarkers was performed. The results showed that tau PET was in good agreement with PDC pathology, while SIMOA showed AD changes and was not consistent with PDC pathology.

Academic Significance and Societal Importance of the Research Achievements

紀伊ALS/PDCでは、脳内にタウ、α-synuclein 、TDP-43蛋白が多重蓄積するため、血液中でこれらの蛋白質を検出できれば、臨床研究に向けた生前診断法の確立に結びつけることができる。本研究からは、SIMOAによる血中微量蛋白質の検出結果は、タウPET画像解析結果および脳内病理とは一致しなかった。具体的には、脳内にはないAβが血中で検出された。ALS/PDCでは、脳内病理と血中蛋白質で乖離があるのか、あるいは脳内蛋白質のクリアランスが亢進してAβが蓄積しにくいメカニズムがあるのかもしれない。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (37 results)

All 2024 2023 2022 2021 2020 2019 2018 2017 Other

All Journal Article (17 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Questioning the cycad theory of Kii ALS/PDC causation.2024

    • Author(s)
      Yasumasa Kokubo, Satoru Morimoto, and Mari Yoshida
    • Journal Title

      Nature review neurology

      Volume: 20 Issue: 3 Pages: 194-194

    • DOI

      10.1038/s41582-024-00936-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tau Filaments from Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia (ALS/PDC) adopt the CTE Fold.2023

    • Author(s)
      Chao Qi, Bert M Verheijen, Yasumasa Kokubo, Yang Shi, Stephan Tetter, Alexey G. Murzin, Asa Nakahara, Satoru Morimoto, Marc Vermulst, Ryogen Sasaki, Eleonora Aronica, Yoshifumi Hirokawa, Kiyomitsu Oyanagi, Akiyoshi Kakita, Benjamin Ryskeldi-Falcon, Mari Yoshida, Masato Hasegawa, Sjors H W Scheres, Michel Goedert.
    • Journal Title

      PNAS

      Volume: 120 Issue: 51

    • DOI

      10.1073/pnas.2306767120

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 紀伊 ALS2023

    • Author(s)
      小久保康昌
    • Journal Title

      Clinical Neuroscience

      Volume: 41 Pages: 322-324

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amyotrophic Lateral Sclerosis / Parkinsonism-Dementia Complex (ALS/PDC) in the Kii peninsula of Japan. -As a tauopathy -2023

    • Author(s)
      Yasumasa Kokubo
    • Journal Title

      Guam Medical Journal

      Volume: 3 Pages: 60-63

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Protein profiling of extracellular vesicles from iPSC-derived astrocytes of patients with ALS/PDC in Kii peninsula2023

    • Author(s)
      Kobayashi Hiroya、Ueda Koji、Morimoto Satoru、Ishikawa Mitsuru、Leventoux Nicolas、Sasaki Ryogen、Hirokawa Yoshifumi、Kokubo Yasumasa、Okano Hideyuki
    • Journal Title

      Neurological Sciences

      Volume: 44 Issue: 12 Pages: 4511-4516

    • DOI

      10.1007/s10072-023-07000-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] APOE alleles with tau and A pathology in patients with amyotrophic lateral sclerosis and parkinsonism-dementia complex in Kii peninsula2022

    • Author(s)
      Ryogen Sasaki, Satoru Morimoto, Fumiko Ozawa, Hideyuki Okano, Mari Yoshida, Hiroyuki Ishiura, Shoji Tsuji, Shigeki Kuzuhara, and Yasumasa Kokubo
    • Journal Title

      Neurology

      Volume: 99 Issue: 22

    • DOI

      10.1212/wnl.0000000000201156

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An immigrant family with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex2021

    • Author(s)
      Kokubo Y, Morimoto S, Sasaki R, Hasegawa M, Ishiura H, Tsuji S, Yoshida M, Yamazoe N, Miyazaki M, Kuzuhara S.
    • Journal Title

      Neurol Sci.

      Volume: 43(2) Issue: 2 Pages: 1423-1425

    • DOI

      10.1007/s10072-021-05737-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Extensive-stage Small-cell Lung Cancer Case With Preexisting Lambert-Eaton Myasthenic Syndrome Successfully Treated With an Immune Checkpoint Inhibitor2021

    • Author(s)
      Tadashi Sakaguchi, Yasumasa Kokubo, Kazuki Furuhashi, YukiNakamura, Yuta Suzuki, Kentaro Ito, Kentaro Fujiwara, Yoichi Nishii, Osamu Taguchi, Osamu Hataji
    • Journal Title

      Clin Lung Cancer

      Volume: - Issue: 3 Pages: e273-e275

    • DOI

      10.1016/j.cllc.2021.09.001

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 紀伊半島に多発するALSとALS-parkinsonism dementia complex2021

    • Author(s)
      小久保康昌
    • Journal Title

      脳神経内科

      Volume: 95 Pages: 489495-489495

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Brain transcriptome analysis links deficiencies of stress-responsive proteins to the pathomechanism of Kii ALS/PDC2020

    • Author(s)
      Satoru Morimoto, Mitsuru Ishikawa, Hirotaka Watanabe, Miho Isoda, Masaki Takao, Shiho Nakamura, Fumiko Ozawa, Yoshifumi Hirokawa, Shigeki Kuzuhara, Hideyuki Okano, Yasumasa Kokubo
    • Journal Title

      Antioxidants

      Volume: 9 Issue: 5 Pages: 423-423

    • DOI

      10.3390/antiox9050423

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of mutant ubiquitin and proteostasis impairment in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex brains2020

    • Author(s)
      Bert M. Verheijen, Satoru Morimoto, Ryogen Sasaki, Kiyomitsu Oyanagi, Yasumasa Kokubo, Shigeki Kuzuhara, Fred W. van Leeuwen
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 79 Issue: 8 Pages: 902-907

    • DOI

      10.1093/jnen/nlaa056

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 増大特集 ALS2019 紀伊ALS/PDCの現状20192019

    • Author(s)
      小久保康昌
    • Journal Title

      BRAIN and NERVE

      Volume: 71 Issue: 11 Pages: 1236-1244

    • DOI

      10.11477/mf.1416201433

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2019-11-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amyotrophic Lateral Sclerosis / Parkinsonism-Dementia Complex (ALS/PDC) of Guam, West New Guinea, and the Kii peninsula of Japan.2019

    • Author(s)
      Kokubo Yasumasa
    • Journal Title

      Guam Medical Journal

      Volume: 1 Pages: 69-73

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tau imaging detects distinctive distribution of tau pathology in ALS/PDC on the Kii Peninsula2018

    • Author(s)
      Shinotoh Hitoshi、Shimada Hitoshi、Kokubo Yasumasa、Tagai Kenji、Niwa Fumitoshi、Kitamura Soichiro、Endo Hironobu、Ono Maiko、Kimura Yasuyuki、Hirano Shigeki、Mimuro Maya、Ichise Masanori、Sahara Naruhiko、Zhang Ming-Rong、Suhara Tetsuya、Higuchi Makoto
    • Journal Title

      Neurology

      Volume: 92 Issue: 2

    • DOI

      10.1212/wnl.0000000000006736

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan2018

    • Author(s)
      Hata Yukiko、Ma Ning、Yoneda Misao、Morimoto Satoru、Okano Hideyuki、Murayama Shigeo、Kawanishi Shosuke、Kuzuhara Shigeki、Kokubo Yasumasa
    • Journal Title

      Frontiers in Neuroscience

      Volume: 11 Pages: 751-751

    • DOI

      10.3389/fnins.2017.00751

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optineurin pathology in the spinal cord of amyotrophic lateral sclerosis/parkinsonism-dementia complex patients in Kii Peninsula, Japan2018

    • Author(s)
      Morimoto Satoru、Hatsuta Hiroyuki、Motoyama Rie、Kokubo Yasumasa、Ishiura Hiroyuki、Tsuji Shoji、Kuzuhara Shigeki、Murayama Shigeo
    • Journal Title

      Brain Pathology

      Volume: 28 Issue: 3 Pages: 422-426

    • DOI

      10.1111/bpa.12558

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unusual tau pathology of the cerebellum in patients with amyotrophic lateral sclerosis/parkinsonism-dementia complex from the kii peninsula, Japan.2017

    • Author(s)
      Morimoto S, Hatsuta H, Kokubo Y, Nakano Y, Hasegawa M, Yoneda M, Hirokawa Y, Kuzuhara S, Shiraishi T, Murayama S.
    • Journal Title

      Brain Pathol.

      Volume: - Issue: 2 Pages: 287-291

    • DOI

      10.1111/bpa.12500

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Doctor's current practice and perspectives on delivering diagnosis in amyotrophic lateral sclero-sis: An international survey in Asian and Oceanian countries.2023

    • Author(s)
      Miki Yoshitake., Kazumoto Shibuya, Matthew Kiernan...Yasumasa Kokubo21番目, Satoshi Kuwabara.
    • Organizer
      PACTALS
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「疾患概念が拡大するタウオパチーの現在」日本の紀伊半島のALSとパーキンソン認知症複合(PDC)2022

    • Author(s)
      小久保康昌
    • Organizer
      第63回日本神経学会総会学術研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] Kii ALS/PDC患者iPS細胞由来グリアモデルを用いた、エクソソーム中網羅的タンパク質プロファイリング2022

    • Author(s)
      小林博也, 森本 悟, 植田幸嗣, 小久保康昌, 岡野栄之
    • Organizer
      第63回日本神経学会総会学術研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] APOE alleles with tau and Aβ pathology in patients with ALS/PDC in Kii peninsula2022

    • Author(s)
      Satoru Morimoto, Ryogen Sasaki, Fumiko Ozawa, Hideyuki Okano, Mari Yoshida, Hiroyuki Ishiura, Shoji Tsuji, Shigeki Kuzuhara, Yasumasa Kokubo
    • Organizer
      第41回日本認知症学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Kii ALS/PDCアストロサイト由来エクソソーム中タンパク質の特異性2022

    • Author(s)
      小林博也, 森本 悟, 植田幸嗣, 小久保康昌, 岡野栄之
    • Organizer
      第41回日本認知症学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 紀伊半島の筋萎縮性側索硬化症/パーキンソン認知症複合患者のAPOEε2対立遺伝子はタウ病理と関連する2022

    • Author(s)
      森本悟, 佐々木良元,小澤史子, 岡野栄之, 吉田眞理, 石浦浩之, 辻省次, 葛原茂樹, 小久保康昌
    • Organizer
      第65回日本脳循環代謝学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Expression of mutant ubiquitin and proteostasis impairment in Kii ALS/PDC2020

    • Author(s)
      Yasumasa Kokubo,Bert M. Verheijen, Satoru Morimoto, Ryogen Sasaki,Kiyomitsu Oyanagi, Shigeki Kuzuhara, Fred W. van Leeuwen
    • Organizer
      第61回日本神経病理学会総会学術研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Medical manual for Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism-dementia complex (PDC) of the Kii peninsula of Japan2020

    • Author(s)
      Y. Kokubo, S. Morimoto, R. Sasaki, K Kanai, K Okamoto, T Kihira, S. Kuzuhara
    • Organizer
      第61回日本神経学会総会学術研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Abnormal Accumulation of Citrullinated Proteins of Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism-dementia complex (PDC) of the Kii peninsula of Japan.2019

    • Author(s)
      Y. Kokubo, S. Morimoto, R. Sasaki, S. Kuzuhara, A. Ishigami.
    • Organizer
      30th International Symposium on ALS/MND
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 紀伊半島南部ALS多発地域のALS患者における血中酸化ストレスマーカーの検討2019

    • Author(s)
      荒川裕也、伊藤俊次、石口宏、河本純子、廣西昌也、伊東秀文、小久保康昌、紀平為子.
    • Organizer
      第59回日本臨床化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Abnormal Accumulation of Citrullinated Proteins of Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism-dementia complex (PDC) of the Kii peninsula of Japan.2019

    • Author(s)
      Y. Kokubo, S. Morimoto, R. Sasaki, S. Kuzuhara, A. Ishigami.
    • Organizer
      第13回MDSJ
    • Related Report
      2019 Research-status Report
  • [Presentation] Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex in the Kii Peninsula2019

    • Author(s)
      Yasumasa Kokubo
    • Organizer
      6th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Abnormal Accumulation of Citrullinated Proteins of Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism-dementia complex (PDC) of the Kii peninsula of Japan2019

    • Author(s)
      Y. Kokubo, S. Morimoto, R. Sasaki, S. Kuzuhara, A. Ishigami.
    • Organizer
      第60回日本神経学会総会学術研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] A Clinical Manual of Amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) of the Kii peninsula of Japan.2018

    • Author(s)
      Y. Kokubo, S. Morimoto, R. Sasaki, K Kanai, K Okamoto, T Kihira, S. Kuzuhara.
    • Organizer
      第59回日本神経学会総会学術研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] the three subtypes in Kii ALS/PDC of the H focus : clinicopathological differences of each subtype.2018

    • Author(s)
      Maya Mimuro, Mari Yoshida, Ryogen Sasaki, Keita Sakurai, Masato Hasegawa, Shigeki Kuzuhara, Yasumasa Kokubo.
    • Organizer
      第59回日本神経学会総会学術研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 紀伊半島の筋萎縮性側索硬化症/パーキンソン認知症複合における末梢神経軸索興奮性変化2018

    • Author(s)
      網野寛、澁谷和幹、三澤園子、関口縁、水地智基、常山篤子、鈴木陽一、島田斉、小久保康昌、桑原聡.
    • Organizer
      第48回日本臨床神経生理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Hohara focus of the Kii Peninsula : pathological findings as a multiple proteinopathy2018

    • Author(s)
      Maya Mimuro, Mari Yoshida, Yasushi Iwasaki, Ryogen Sasaki, Shigeki Kuzuhara, Yasumasa Kokubo.
    • Organizer
      19th International Congress of Neuropathology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 紀伊半島の筋萎縮性側索硬化症・パーキンソン/認知症複合-Kii ALS/PDC

    • URL

      http://kii-als-pdc-project.com

    • Related Report
      2023 Annual Research Report
  • [Remarks] 紀伊半島の筋萎縮性総索硬化症/パーキンソン認知症複合 -Kii ALS/PDC

    • URL

      http://kii-als-pdc-project.com

    • Related Report
      2022 Research-status Report 2021 Research-status Report 2020 Research-status Report
  • [Remarks] 紀伊半島の筋萎縮性総索硬化症/パーキンソ ン認知症複合 -Kii ALS/PDC

    • URL

      http://kii-als-pdc-project.com

    • Related Report
      2019 Research-status Report 2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi