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November 29, 2022; 99 (22) Research Article

APOE Alleles With Tau and Aβ Pathology in Patients With Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex in the Kii Peninsula

Ryogen Sasaki, Satoru Morimoto, Fumiko Ozawa, View ORCID ProfileHideyuki Okano, Mari Yoshida, View ORCID ProfileHiroyuki Ishiura, Shoji Tsuji, Shigeki Kuzuhara, Yasumasa Kokubo
First published September 21, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201156
Ryogen Sasaki
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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Satoru Morimoto
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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Fumiko Ozawa
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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Hideyuki Okano
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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  • ORCID record for Hideyuki Okano
Mari Yoshida
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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Hiroyuki Ishiura
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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  • ORCID record for Hiroyuki Ishiura
Shoji Tsuji
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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Shigeki Kuzuhara
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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Yasumasa Kokubo
From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
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APOE Alleles With Tau and Aβ Pathology in Patients With Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex in the Kii Peninsula
Ryogen Sasaki, Satoru Morimoto, Fumiko Ozawa, Hideyuki Okano, Mari Yoshida, Hiroyuki Ishiura, Shoji Tsuji, Shigeki Kuzuhara, Yasumasa Kokubo
Neurology Nov 2022, 99 (22) e2437-e2442; DOI: 10.1212/WNL.0000000000201156

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Article Information

vol. 99 no. 22 e2437-e2442
DOI: 
https://doi.org/10.1212/WNL.0000000000201156
PubMed: 
36130843

Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received November 16, 2021
  • Accepted in final form July 11, 2022
  • First Published September 21, 2022.

Article Versions

  • Previous version (September 21, 2022 - 12:48).
  • You are viewing the most recent version of this article.
Copyright & Usage: 
© 2022 American Academy of Neurology

Author Disclosures

    1. Ryogen Sasaki, MD, PhD,
    2. Satoru Morimoto, MD, PhD,
    3. Fumiko Ozawa,
    4. Hideyuki Okano, MD, PhD,
    5. Mari Yoshida, MD, PhD,
    6. Hiroyuki Ishiura, MD, PhD,
    7. Shoji Tsuji, MD,
    8. Shigeki Kuzuhara, MD, PhD and
    9. Yasumasa Kokubo, MD, PhD
  1. Ryogen Sasaki, MD, PhD,
  2. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  3. Satoru Morimoto, MD, PhD,
  4. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  5. Fumiko Ozawa,
  6. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  7. Hideyuki Okano, MD, PhD,
  8. Scientific Advisory Boards:
    1. (1) SanBio Co. Ltd; (2) K Pharma Co. Ltd.; (3) Kringle Pharma Inc.

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. (1) Inflammation and Regeneration, Editor-in-Chief, 2004~2022. (2) Stem Cell Reports, Editorial Board, 2017~2022. (3) Cell Stem Cell, Editorial Board, 2006~2022 (4) Genes to Cells, Associate Editor, 2008~2022

    Patents:
    1. 1. METHOD FOR PRODUCING ASTROCYTES, S Morimoto, Z Zhou, H Okano - US Patent App. 17/275,395, 2022. 2. Sample preparation system and method for electron microscope observation, plasma treatment apparatus, sputtering apparatus, and tape feeding mechanism used for sample preparation, S Shibata, T Shindo, H Okano, S Goto, US Patent App. 17/417,451, 2022. 3.METHOD FOR PRODUCING BRAIN ORGANOIDS, H Hiramine, M Ishikawa, H Okano, US Patent App. 17/293,355, 2022. 4. Suicide gene therapeutic agent for brain tumors using pluripotent stem cell, M Toda, H Okano, H Miyoshi, R Tamura, US Patent App. 16/765,257, 2022. 5.Treating Hearing Loss, A Edge, H Okano, M Fujioka, K Mizutari - US Patent App. 17/118,111, 2021.

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. (1)Takeda Pharmaceutical Company

    Research Support, Government Entities:
    1. (1) AMED, JP 22bm0804003, Principal Investigator, 2022

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. (1) Japanese Society for Regenerative Medicine (2) Japanese Society for Neurochemistry

    Stock/Stock Options/Board of Directors Compensation:
    1. (1) K Pharma Co. Ltd

    License Fee Payments, Technology or Inventions:
    1. (1) Sumitomo Pharmaceutical Co. Ltd

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. (1) SanBio Co. Ltd

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  9. Mari Yoshida, MD, PhD,
  10. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  11. Hiroyuki Ishiura, MD, PhD,
  12. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. (1) Speaker honoraria from Eisai Co., Ltd., FP Pharmaceutical Corporation, Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., UCB Japan Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Daiichi Sankyo Co., Ltd. (2) Speaker honoraria from Asian-Oceanian Myology Center and Korean Society of Medical Genetics and Genomics.

    Editorial Boards:
    1. Editorial Board of Journal of Human Genetics (2020-) and Clinical Neurology (2021-).

    Patents:
    1. Patents pending on genetic analysis of benign adult familial myoclonus epilepsy and CGG repeat expansion diseases.

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. Funds from the the Japan Society for the Promotion of Science (17H05085, 2017-2020; 18K19506, 2018-2020; and 20H03588 2020-2023).

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. Funds from the Kato Memorial Trust for Nambyo Research and Life Science Foundation of Japan.

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  13. Shoji Tsuji, MD,
  14. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. Ono Pharmaceutical Co. Ltd. Sanofi Novartis Japan Senju Pharmaceutical Co. Ltd.

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. Ono Pharmaceutical Co. Ltd.

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. Nobelpharma Co. Ltd.

    Research Support, Government Entities:
    1. The Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI [19H03425]), and the Japan Agency for Medical Research and Development (Grant-in-Aid [21ek0109491h0002]).

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  15. Shigeki Kuzuhara, MD, PhD and
  16. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  17. Yasumasa Kokubo, MD, PhD
  18. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. (1) the Research Committee of CNS Degenerative Diseases (to YK, H29-Nanchi- Ippan-085, collaborator, 2017 - 2019) (2) the Research Committee of Muro Disease (Kii ALS/PDC) (to YK, 21210301, Chair, 2009-2014), by the Ministry of Health, Labor and Welfare (MHLW), Japan, (3) JSPS KAKENHI Grant Number (to YK, JP25305030, JP18KK0239, JP17H01689, JP18K07368, JP15J03921, JP19K17002, JP15K09364, JP18K07514, to SM, 19K17002, Chair, 2019–) (4) agrant-in-aid of the Research Consortium of Kii ALS/PDC from the Japan Agency for Medical Research and Development, AMED (to YK, 17ek0109139h0003, Chair, 2015-2017)

    Research Support, Academic Entities:
    1. (1) the Mie Medical Fund, Japan (2) Japan Foundation for Neuroscience and Mental Health

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  1. From the School of Nursing (R.S.), Suzuka University of Medical Science; Department of Physiology (S.M., F.O., H.O.), Keio University School of Medicine, Tokyo; Department of Oncologic Pathology (S.M.), School of Medicine, Mie University, Tsu; Department of Neuropathology (M.Y.), Institute for Medical Science of Aging, Aichi Medical University, Nagakute; Department of Neurology (H.I.), Graduate School of Medicine, the University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, the University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare; Graduate School of Health Science and School of Nursing (S.K.), Suzuka University of Medical Science; and Kii ALS/PDC Research Center (Y.K.), Mie University, Graduate School of Regional Innovation Studies, Tsu, Japan.
  1. Correspondence
    Dr. Kokubo ktyktykty{at}me.com
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