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Tauopathy affecting astrocytes: diversity in the tau pathology and the astrocytic molecular feature

Research Project

Project/Area Number 17H03554
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionNiigata University

Principal Investigator

Takahashi Hitoshi  新潟大学, 脳研究所, 非常勤講師 (90206839)

Co-Investigator(Kenkyū-buntansha) 小野寺 理  新潟大学, 脳研究所, 教授 (20303167)
加藤 泰介  新潟大学, 脳研究所, 特任准教授 (30598496)
田中 英智  新潟大学, 脳研究所, 特別研究員 (80612225)
豊島 靖子  新潟大学, 脳研究所, 准教授 (20334675)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsタウオパチー / アストロサイト / 4-リピートタウ / 進行性核上性麻痺 / 皮質基底核変性症 / globular glial tauopathy / 4-リピートタウ / Globular glial tauopathy
Outline of Final Research Achievements

Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised by tau-positive globular glial inclusions, such as globular astrocytic inclusions (GAIs).Neuropathologically, we identified 6 cases of GTT and classified 3 and 3 cases into Type II and Type III, respectively. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than Type II. Neuronal cytoplasmic inclusions (NCIs) were divisible into three subgroups in terms of shape: diffuse granular, thick-cord-like, and round/horseshoe-shaped structures.Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. These findings indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.

Academic Significance and Societal Importance of the Research Achievements

本研究は神経変性疾患の病的蛋白のひとつであるタウを扱ったものある。今日、世界的にもPSPやCBDの臨床診断の確立、その病理学的研究の推進が望まれている。我々は、PSPやCBDの研究と併せ、世界に先駆けて、アストロサイト胞体内に4-リピートタウの蓄積を特徴とする新たな疾患の存在を報告してきた。今回、それらの症例も含め、globular glial tauopathyの6例 (Type II、3例;Type III:3例)の病理学、生化学、そしてタウ遺伝子の解析を行なった。本邦では、高齢・超高齢化社会の克服はまさにこれからという時代、認知症・運動障害に関わる神経変性疾患研究の重要性は言を俟たない。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (18 results)

All 2020 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Morphological characterization of glial and neuronal tau pathology in globular glial tauopathy (Types II and III)2020

    • Author(s)
      Tanaka H, Toyoshima Y, Kawakatsu S, Kobayashi R, Yokota O, Terada S, Kuroda S, Miura T, Higuchi Y, Otsu H, Sanpei K, Otani K, Ikeuchi T, Onodera O, Kakita A, Takahashi H
    • Journal Title

      Neuropathol Appl Neurobiol

      Volume: 46 Pages: 344-358

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amyotrophic lateral sclerosis with pallidonigroluysian degeneration: a clinicopathological study2020

    • Author(s)
      Ito J, Shimizu H, Ohta K, Idezuka J, Tanaka H, Kondo H, Nakajima T, Takahashi H, Akazawa K, Onodera O, Kakita A
    • Journal Title

      Ann Neurol

      Volume: 87 Issue: 2 Pages: 302-312

    • DOI

      10.1002/ana.25652

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 前頭側頭葉変性症の神経病理学2019

    • Author(s)
      豊島靖子, 高橋 均
    • Journal Title

      老年精神医学雑誌

      Volume: 30 Pages: 1080-1088

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Globular glial tauopathy Type II: Clinicopathological study of two autopsy cases2019

    • Author(s)
      Tanaka Hidetomo、Kawakatsu Shinobu、Toyoshima Yasuko、Miura Takeshi、Mezaki Naomi、Mano Atsushi、Sanpei Kazuhiro、Kobayashi Ryota、Hayashi Hiroshi、Otani Koichi、Ikeuchi Takeshi、Onodera Osamu、Kakita Akiyoshi、Takahashi Hitoshi
    • Journal Title

      Neuropathology

      Volume: 39 Issue: 2 Pages: 111-119

    • DOI

      10.1111/neup.12532

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Globular glial tauopathy の神経病理2018

    • Author(s)
      田中 英智, 豊島 靖子, 柿田 明美
    • Journal Title

      神経内科

      Volume: 88 Pages: 477-482

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).2017

    • Author(s)
      Kovacs GG, Bigio EH, Budka H, Dickson DW, Ferrer I, Forrest SL, Gelpi E, Gentleman SM, Giaccone G, Grinberg LT, Halliday GM, Hatanpaa KJ, Hof PR, Hofer M, Ironside JW, King A, Kofler J, Kril JJ, Love S, Mackenzie IR, Mao Q, Matej R, McLean C, Munoz DG, Murray ME, Takahashi H, et al
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 76 Issue: 7 Pages: 605-619

    • DOI

      10.1093/jnen/nlx041

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PLA2G6 accumulates in Lewy bodies in PARK14 and idiopathic Parkinson's disease.2017

    • Author(s)
      Miki Y, Tanji K, Mori F, Kakita A, Takahashi H, Wakabayashi K.
    • Journal Title

      Neurosci Lett

      Volume: 645 Pages: 40-45

    • DOI

      10.1016/j.neulet.2017.02.027

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Alteration of mitochondrial protein PDHA1 in Lewy body disease and PARK14.2017

    • Author(s)
      Miki Y, Tanji K, Mori F, Kakita A, Takahashi H, Wakabayashi K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 489 Issue: 4 Pages: 439-444

    • DOI

      10.1016/j.bbrc.2017.05.162

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Familial amyotrophic lateral sclerosis with an I104F mutation in the SOD1 gene: multisystem degeneration with neurofilamentous aggregates and SOD1 inclusions.2017

    • Author(s)
      Jiang H, Shimizu H, Shiga A, Tanaka M, Onodera O, Kakita A, Takahashi H.
    • Journal Title

      Neuropathology

      Volume: 37 Issue: 1 Pages: 69-77

    • DOI

      10.1111/neup.12324

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] GPNMB ameliorates mutant TDP-43-induced motor neuron cell death.2017

    • Author(s)
      Nagahara Y, Shimazawa M, Ohuchi K, Ito J, Takahashi H, Tsuruma K, Kakita A, Hara H
    • Journal Title

      J Neurosci Res

      Volume: 95 Issue: 8 Pages: 1647-1665

    • DOI

      10.1002/jnr.23999

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy.2017

    • Author(s)
      Inoue Y, Ueda M, Tasaki M, Takeshima A, Nagatoshi A, Masuda T, Misumi Y, Kosaka T, Nomura T, Mizukami M, Matsumoto S, Yamashita T, Takahashi H, Kakita A, Ando Y.
    • Journal Title

      Acta Neuropathologica

      Volume: 134 Issue: 4 Pages: 605-617

    • DOI

      10.1007/s00401-017-1720-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 進行性核上性麻痺の排尿障害:橋被蓋corticotropin-releasing factor 陽性細胞の脱落の検討2019

    • Author(s)
      豊島靖子, 井樋慶一, 田中英智, 齋藤理恵, 清水 宏, 芝崎 保, 大原慎司, 高橋 均, 柿田明美
    • Organizer
      日本神経病理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Morphological features of neuronal and glial tau pathology in GGT (Types II and III)2019

    • Author(s)
      Tanaka H, Toyoshima Y, Kawakatsu S, Miura T, Ikeuchi T, Onodera O, Takahashi H, Kakita A
    • Organizer
      19th International Congress of Neuropathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] “CORRECT” for introducing nucleotide substitution with CRISPR/Cas9 system in MAPT gene.2017

    • Author(s)
      Koike Y, Koyama A, Shiga A, Yokoseki A, Onodera O
    • Organizer
      The 23rd World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] “CORRECT” for introducing nucleotide substitution with CRISPR/Cas9 system in MAPT gene2017

    • Author(s)
      Koike Y, Koyama A, Shiga A, Yokoseki A, Onodera O
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cerebral TDP-43 pathology in amyotrophic lateral sclerosis.2017

    • Author(s)
      Takahashi H
    • Organizer
      The 10th Congress of Asia Pacific International Academy of Pathology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 進行性核上性麻痺:短期経過剖検例の病理組織学的検討.2017

    • Author(s)
      張 路, 豊島靖子, 柿田明美, 小野寺 理, 高橋 均
    • Organizer
      第58回日本神経病理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Pick 病のアストロサイトには脱アミド化 4 リピートタウが蓄積する.2017

    • Author(s)
      田中英智, 豊島靖子, 他田真理, 清水 宏, 高橋 均, 柿田明美
    • Organizer
      第58回日本神経病理学会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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