Washout of Accumulated Abnormal Proteins via Glymphatic System
| Project/Area Number |
18K07507
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Osaka City University |
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Principal Investigator |
Itoh Yoshiaki 大阪市立大学, 大学院医学研究科, 教授 (90265786)
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(32 results)
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[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.
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Journal Title
Int J Mol Sci.
Volume: 21
Issue: 12
Pages: 4443-4443
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Frontiers in Aging Neuroscience
Volume: 11
Pages: 222-222
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Microcirculation
Volume: 26
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Neurol Sci
Volume: 39
Pages: 1597-1602
Related Report
Peer Reviewed
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[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
Int'l Joint Research
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