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

Washout of Accumulated Abnormal Proteins via Glymphatic System

Research Project

Project/Area Number 18K07507
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionOsaka City University

Principal Investigator

Itoh Yoshiaki  大阪市立大学, 大学院医学研究科, 教授 (90265786)

Co-Investigator(Kenkyū-buntansha) 安部 貴人  大阪市立大学, 大学院医学研究科, 准教授 (30365233)
武田 景敏  大阪市立大学, 大学院医学研究科, 講師 (90445015)
竹内 潤  大阪市立大学, 大学院医学研究科, 医員 (20771819)
三野 俊和  大阪市立大学, 大学院医学研究科, 病院講師 (60597566)
長谷川 樹  大阪市立大学, 大学院医学研究科, 医員 (90793753)
木村 裕子  大阪市立大学, 大学院医学研究科, 後期臨床研究医 (20815394)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsアミロイドβ / アルツハイマー病 / 血管周囲腔 / 認知症治療 / 認知症 / 多光子顕微鏡 / アストロサイト / glymphatic系 / ネットワーク / エンドフット / アミロイドベータ / タウ蛋白 / Glymphatic系 / アルツハイマー
Outline of Final Research Achievements

We successfully identified the perivascular space as one of the washing-out route of amyloid beta, the causative substance of Alzheimer disease. In the experiment, we observed that amyloid beta, applied on the surface of the cerebral cortex, was transferred gradually in the space along the penetrating vessels. We used live imaging system with cover glass on the top of the cerebral cortex and a two-photon microscopy. The passage of amyloid beta was localized to a segment of perivascular space. In the clinical setting, amyloid beta is thought to be cut from the neurons and washed-out from the deep parenchyma through this perivascular space in the direction opposite to the observed flow and disturbance of this clearance may trigger the development of Alzheimer's disease.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病の原因物質であるアミロイドβの排出経路を突き止めた研究です。現在アルツハイマー病には根本的な治療法がなく、アミロイドβに対する抗体療法によって脳内アミロイドを低下させ、認知症の進行抑制、発症予防ができないか検討されています。抗体療法の問題の一つがARIAと呼ばれる血管の炎症と脳浮腫で、これが起きると折角アミロイドを低下させても認知症が悪化します。今回の我々の研究は別の角度からアミロイドβを低下させる可能性が示唆され、今後の治療法開発に期待されています。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (32 results)

All 2020 2019 2018 Other

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation.2020

    • Author(s)
      Hiroyuki Shimada, Shinobu Minatani, Jun Takeuchi, Akitoshi Takeda, Joji Kawabe, Yasuhiro Wada, Aya Mawatari, Yasuyoshi Watanabe, Hitoshi Shimada, Makoto Higuchi, Tetsuya Suhara, Takami Tomiyama, Yoshiaki Itoh.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 12 Pages: 4443-4443

    • DOI

      10.3390/ijms21124443

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of Creutzfeldt-Jakob disease with stroke-like onset2020

    • Author(s)
      Okamoto K, Abe T, Itoh Y
    • Journal Title

      J Stroke Cerebrovasc Dis .

      Volume: 29 Issue: 6 Pages: 104788-104788

    • DOI

      10.1016/j.jstrokecerebrovasdis.2020.104788

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and Risk Factors of Silent Brain Infarction in Patients with Aortic Stenosis2020

    • Author(s)
      Ito Ayaka、Iwata Shinichi、Tamura Soichiro、Kim Andrew T、Nonin Shinichi、Ishikawa Sera、Ito Asahiro、Izumiya Yasuhiro、Abe Takato、Shibata Toshihiko、Yoshiyama Minoru
    • Journal Title

      Cerebrovascular Diseases Extra

      Volume: 10 Issue: 3 Pages: 116-123

    • DOI

      10.1159/000510438

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amyloid-Negative Dementia in the Elderly is Associated with High Accumulation of Tau in the Temporal Lobes2019

    • Author(s)
      Takeuchi Jun、Kikukawa Takayuki、Saito Haruna、Hasegawa Itsuki、Takeda Akitoshi、Hatsuta Hiroyuki、Kawabe Joji、Wada Yasuhiro、Mawatari Aya、Igesaka Ami、Doi Hisashi、Watanabe Yasuyoshi、Shimada Hitoshi、Kitamura Soichiro、Higuchi Makoto、Suhara Tetsuya、Itoh Yoshiaki
    • Journal Title

      The Open Biomedical Engineering Journal

      Volume: 13 Issue: 1 Pages: 55-66

    • DOI

      10.2174/1874120701913010055

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Staging of tau distribution by positron emission tomography may be useful in clinical staging of Alzheimer disease2019

    • Author(s)
      Kenta Aohara,Shinobu Minatani,Hiroko Kimura,Jun Takeuchi,Akitoshi Takeda,Joji Kawabe,Yasuhiro Wada,Aya Mawatari,Yasuyoshi Watanabe,Hitoshi Shimada,Makoto Higuchi,Tetsuya Suhara,Yoshiaki Itoh.
    • Journal Title

      Neurology and Clinical Neurocience

      Volume: 8 Issue: 2 Pages: 61-67

    • DOI

      10.1111/ncn3.12366

    • NAID

      120007007732

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020114

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects2019

    • Author(s)
      Ming-Jang Chiu, Lih-Fen Lue, Ming-Chyi Pai, Ta-Fu Chen, Chaur-Jong Hu, Likai Huang, Wei-Che Lin, Chau-Chung Wu, Jiann-Shing Jeng, Kaj Blennow, Marwan N Sabbagh, Sui-Hing Yan, Pei-Ning Wang, Shieh-Yueh Yang, Hiroyuki Hatsuta, Satoru Morimoto, Akitoshi Takeda, Yoshiaki Itoh, Jun Liu, Haiqun Xie
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 11 Pages: 222-222

    • DOI

      10.3389/fnagi.2019.00222

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spatiotemporal dynamics of red blood cells in capillaries in layer I of the cerebral cortex and changes in arterial diameter during cortical spreading depression and response to hypercapnia in anesthetized mice.2019

    • Author(s)
      Unekawa M, Tomita Y, Toriumi H, Osada T, Masamoto K, Kawaguchi H, Izawa Y, Itoh Y, Kanno I, Suzuki N, Nakahara J
    • Journal Title

      Microcirculation

      Volume: 26 Issue: 6

    • DOI

      10.1111/micc.12552

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relationship Turmoil and Emotional Empathy in Frontotemporal Dementia.2019

    • Author(s)
      Takeda A, Sturm VE, Rankin KP, Ketelle R, Miller BL, Perry DC
    • Journal Title

      Alzheimer Dis Assoc Disord

      Volume: 51 Issue: 3 Pages: 1222-1232

    • DOI

      10.1097/wad.0000000000000317

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex2018

    • Author(s)
      Hasegawa Itsuki、Takeda Akitoshi、Hatsuta Hiroyuki、Kubo Yuki、Ohsawa Masahiko、Nakano Yuta、Ikeuchi Takeshi、Hasegawa Masato、Murayama Shigeo、Itoh Yoshiaki
    • Journal Title

      Neuropathology

      Volume: 38 Issue: 4 Pages: 372-379

    • DOI

      10.1111/neup.12457

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rivaroxaban Promotes Reduction of Embolus Size within Cerebrocortical Microvessels in a Mouse Model of Embolic Stroke.2018

    • Author(s)
      Katsumata M, Oki K, Tsukada N, Abe T, Itoh Y, Takahashi S, Suzuki N.
    • Journal Title

      Keio J Med

      Volume: -

    • NAID

      130007711143

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diameter of fluorescent microspheres determines their distribution throughout the cortical watershed area in mice.2018

    • Author(s)
      Naoki Tsukada, Masahiro Katsumata, Koichi Oki, Takato Abe, Shinichi Takahashi, Yoshiaki Itoh, Norihiro Suzuki.
    • Journal Title

      Brain Res.

      Volume: 1679 Pages: 109-115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amyloid deposition and CBF patterns predict conversion of mild cognitive impairment to dementia.2018

    • Author(s)
      Kikukawa T, Abe T, Ataka S, Saito H, Hasegawa I, Mino T, Takeuchi J, Kawabe J, Wada Y, Watanabe Y, Itoh Y.
    • Journal Title

      Neurol Sci

      Volume: 39 Pages: 1597-1602

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 繰り返す脳梗塞に閉塞性水頭症と脳幹萎縮を併発した神経サルコイドーシスの1例.2018

    • Author(s)
      木村裕子、竹内潤、蔦田強司、大畑建治、大澤政彦、伊藤義彰.
    • Journal Title

      臨床神経学

      Volume: 58 Pages: 445-451

    • NAID

      130007420204

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] The effects of PCSK9 inhibitor on apolipoproteins in patients with large artery atherosclerosis2020

    • Author(s)
      Itsuki Hasegawa, Kousuke Okamoto, Takato Abe, Yoshiaki Itoh.
    • Organizer
      ESO-WSO Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] レビー小体型認知症(DLB)の前駆状態と考えられた4例の神経心理学的検討2020

    • Author(s)
      武田景敏, 皆谷忍, 伊藤義彰.
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Intercellular transport of Amyloid β in vivo Observed with Multiphoton Microscopy.2020

    • Author(s)
      Itsuki Hasegawa, Norie Kimura, Shinobu Minatani, Takato Abe, Yoshiaki Itoh
    • Organizer
      第45回日本微小循環学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 神経軸索スフェロイド形成を伴う遺伝性びまん性白質脳症(HDLS)における脳血流SPECT所見の検討2020

    • Author(s)
      長谷川樹, 安部貴人, 伊藤義彰
    • Organizer
      第63回日本脳循環代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アルツハイマー病とGlymphatic系2019

    • Author(s)
      伊藤義彰、平良庸子、澤田礼子、長谷川樹、安部貴人
    • Organizer
      第44回日本脳卒中学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 死亡時92歳の進行性核上性麻痺(PSP)生前同意剖検例2019

    • Author(s)
      初田裕幸、武田景敏、伊藤義彰、桑江優子、大澤雅彦、松原知康、村山繁雄
    • Organizer
      第19回日本神経病理学会近畿地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] In vivo dynamics of amyloid β in glymphatic system observed with multiphoton microscopy2019

    • Author(s)
      Itsuki Hasegawa, Reiko Sawada, Shinobu Minatani, Takato Abe, Yoshiaki Itoh
    • Organizer
      BRAIN&BRAIN PET 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cerebral Microcirculation and Glymphatic System2019

    • Author(s)
      Yoshiaki Itoh
    • Organizer
      The 44th Annual Meeting of Japanese Society for Microcirculation
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 進行性失語症患者における言語機能の神経基盤-FDG-PETの脳糖代謝低下部位との相関-2019

    • Author(s)
      武田景敏、竹内潤、皆谷忍、水田秀子、東山滋明、河邉譲治、伊藤義彰
    • Organizer
      認知症学会2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 磁化率強調画像(SWI)および病理学的に後頭葉の鉄沈着を確認しえた進行性多巣性白質脳症(PML)の一剖検例2019

    • Author(s)
      初田裕幸、諸岡千暁、岡本光祐、武田景敏、大畑麻衣、大澤政彦、三木幸雄、伊藤義彰
    • Organizer
      第20回日本神経病理学会近畿地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] 「脳微小循環とGlymphatic系」2019

    • Author(s)
      伊藤義彰
    • Organizer
      日本微小循環学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 「脳卒中急性期の病態と治療」2019

    • Author(s)
      伊藤義彰
    • Organizer
      日本神経学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 「アルツハイマー病とGlymphatic」2019

    • Author(s)
      伊藤義彰
    • Organizer
      日本脳卒中学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 「脳梗塞治療への実験的アプローチ」2018

    • Author(s)
      伊藤義彰
    • Organizer
      日本神経学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 「脳卒中の予防と慢性期治療」2018

    • Author(s)
      伊藤義彰
    • Organizer
      日本神経学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 36.Amyloid-negative dementia in the elderly is associated with very heavy accumulation of tau in the parietal lobes.2018

    • Author(s)
      Itoh Y, Takeuchi J, Kikukawa T, Saito H, Hasegawa I, Takeda A, Hatsuta H, Kawabe J, Wada Y, Mawatari A, Igesaka A, Doi H, Watanabe Y, Shimada H, Kitamura S, Higuchi M, Suhara T
    • Organizer
      CME2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 症例から学ぶ戦略的急性期脳卒中診断・治療2019

    • Author(s)
      伊藤義彰
    • Total Pages
      254
    • Publisher
      南山堂
    • ISBN
      9784525249311
    • Related Report
      2018 Research-status Report
  • [Book] 脳卒中エキスパート抗血栓療法を究める2019

    • Author(s)
      伊藤義彰
    • Total Pages
      243
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report
  • [Remarks] 大阪市立大学大学院医学系研究科脳神経内科業績

    • URL

      http://www.med.osaka-cu.ac.jp/Neurology/achievements.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi