Elucidation of the role of glial cell in tau transmission and axonal degeneration in Alzheimer's disease and targeted therapy with glial cell
Project/Area Number |
17K09757
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Kyushu University |
Principal Investigator |
Asai Hirohide 九州大学, 医学研究院, 共同研究員 (50510210)
|
Co-Investigator(Kenkyū-buntansha) |
山口 浩雄 九州大学, 大学病院, 特任講師 (00701830)
山崎 亮 九州大学, 医学研究院, 准教授 (10467946)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | アルツハイマー病 / アミロイドβタンパク / ミクログリア / エキソソーム / マイクロRNA / リン酸化タウタンパク / バイオマーカー / CD33 / 毒性アミロイドベータ / 病的タウ / タウ蛋白 / グリア炎症 / 神経科学 |
Outline of Final Research Achievements |
Since exosomes cross the blood-brain barrier, we extracted exosomes from the peripheral blood of APP-KI mouse models of Alzheimer's disease (AD) and attempted to detect toxic turn Aβ42 by dot blotting with success. We extracted microRNAs (miRNAs) from these exosomes and compared AD and wild-type mice by next-generation sequencing, and found that only one miRNA was up-regulated and five miRNAs were down-regulated. These potential blood-based biomarkers may lead to earlier diagnosis as well as new targets for AD treatment. Further analyses using human samples are now under way.
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Academic Significance and Societal Importance of the Research Achievements |
神経細胞以外のアストログリア、オリゴデンドログリア由来のエキソソームも血液中に存在しており、これらのエキソソームの解析によって、軽度認知障害やアルツハイマー病の分子病態の本態が解明される。エキソソームは、血液脳関門を双方向に通過できることから、ドラッグデリバリーとしても利用することかできる。また、同様の細胞特異的エキソソームが腫瘍や免疫疾患などの多くのヒト疾患の分子病態解明につながることへ貢献でき、神経疾患以外においても応用できる可能性がある。
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] Insulin deficiency promotes formation of toxic amyloid-beta42 conformer co-aggregating with hyper-phosphorylated tau oligomer in an Alzheimer's disease model.2020
Author(s)
Imamura T, Yanagihara YT, Ohyagi Y, Nakamura N, Iinuma KM, Yamasaki R, Asai H, Maeda M, Murakami K, Ilie K, Kira JI
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Journal Title
Neurobiology of Disease
Volume: 137
Pages: 104739-104739
DOI
Related Report
Peer Reviewed / Open Access
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