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Vascular dementia: for establishing clinicopathologic diagnostic criteria for small vessel disease

Research Project

Project/Area Number 19K21314
Project/Area Number (Other) 18H06211 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0902:General internal medicine and related fields
Research InstitutionNiigata University

Principal Investigator

Saito Rie  新潟大学, 脳研究所, 助教 (80829078)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脳血管性認知症 / 脳小血管病 / 白質変性 / 血管変性 / 血管走行パターン / 3D蛍光イメージング / small vessel disease / leukoencephalopathy / vessel twisting / vascular dementia / 3D neuropathology / Binswanger病 / 遺伝性脳小血管病 / 3D神経病理 / 診断基準 / 3Dイメージング / 組織透明化 / CADASIL / CARASIL / 3D神経病理
Outline of Research at the Start

血管性認知症の頻度は,アルツハイマー型認知症に次いで多く病態の解明と予防策が急務とされる.特に,脳実質内の小血管を主座とする脳小血管病は,白質変性から認知症を来す血管性認知症の重要な原因の一つでありながら,未だその定義は定まらず,病態は未解明である.本研究では純粋な脳小血管病を有するヒト疾患脳に対して組織透明化による高解像度3D 病理学的解析手法を用いて,認知症の原因となる白質変性の発生機序解明を試みる.また,ミクロな3D 病理像とマクロなMRI 画像及び臨床像を照合することで,脳内の病変の進展様式を明らかにし,”脳ミクロアンギオパチー”の疾患概念の体系化に向けた基盤を
確立する.

Outline of Final Research Achievements

We clarified the different degerative patern of white matter and small vessels in the CNS between reperesentative two small vessel diseases, CADASIl and HTRA1-autosomal dominant disease.

Academic Significance and Societal Importance of the Research Achievements

本研究によって,変性した大脳白質と小血管を2D,3Dで詳細に解析する手法が確立した.これによって,脳小血管病の白質変性に影響する小血管変性パラメーターを同定できた.また,脳小血管病の中には,障害されやすい血管の種類が疾患ごとに異なることを明らかにした.これら病理基盤の解明によって,病因ターゲットが明確となり,より有効な治療法開発への応用が期待される.また,同時に開発された組織透明化による高解像度3Dイメージングは,今後の神経科学の発展に大きく寄与するものとして注目される.

Report

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

    (10 results)

All 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] The diagnosis and management of monogenic cerebral small vessel diseases: Practical guideline by European Academy of Neurology.2020

    • Author(s)
      Saito R, Lioutas VA
    • Journal Title

      Eur J Neurol.

      Volume: - Issue: 7 Pages: 1097-1098

    • DOI

      10.1111/ene.14222

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation.2019

    • Author(s)
      Inoue M, Saito R, Kakita A, Tainaka K.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 29 Issue: 15 Pages: 1886-1890

    • DOI

      10.1016/j.bmcl.2019.05.049

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid clearing of white matter in post-mortem human brain by 1,2-hexanediol delipidation2019

    • Author(s)
      Inoue Masafumi, Rie Saito, Kakita Akiyoshi, Tainaka Kazuki
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters in press

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation2018

    • Author(s)
      Saito Rie、Nozaki Hiroaki、Kato Taisuke、Toyoshima Yasuko、Tanaka Hajime、Tsubata Yutaka、Morioka Tetsuo、Horikawa Yoh、Oyanagi Kiyomitsu、Morita Takashi、Onodera Osamu、Kakita Akiyoshi
    • Journal Title

      Journal of Neuropathology & Experimental Neurology

      Volume: 78 Issue: 2 Pages: 181-186

    • DOI

      10.1093/jnen/nly115

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Small vessel characteristics of autopsied patients with CADASIL and those heterozygous for HTRA1 mutations: 3D analysis using the CUBIC tissue clearing technique2019

    • Author(s)
      Rie Saito, Kazuki Tainaka, Akiyoshi Kakita
    • Organizer
      Amercan Academy of Neurology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 孤発性脳小血管病とCADASIL:剖検脳の白質変性に関する組織像の定量的解析2019

    • Author(s)
      齋藤理恵,鈴木正博,田中政春,野崎洋明,小野寺理,柿田明美
    • Organizer
      神経病理学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CADASILとCARASILヘテロ接合体患者の剖検脳における小血管の特徴:CUBIC組織透明化手法を用いた3D解析2019

    • Author(s)
      齋藤理恵,井上雅文,野崎洋明,田井中一貴,柿田明美
    • Organizer
      神経病理学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CADASIL and CARASIL2018

    • Author(s)
      Rie Saito, Akiyoshi Kakita
    • Organizer
      19th International Congress of Neuropathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Astrocytic features in white matter of patients with CADASIL and Binswanger's disease2018

    • Author(s)
      齋藤理恵,他田真理,柿田明美ら
    • Organizer
      第59回神経学会総会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 新潟大学脳研究所病理学分野研究内容

    • URL

      https://pathology-bri-niigata-u.jp/topics/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report

URL: 

Published: 2018-08-27   Modified: 2024-03-26  

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