Identification of circulating factors triggering molecular pathological processes of Alzheimer's disease
| Project/Area Number |
19K21585
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Studies on the Super-Aging Society
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
Nishimura Masaki 滋賀医科大学, 神経難病研究センター, 教授 (40322739)
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| Project Period (FY) |
2019-06-28 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | アルツハイマー病 / 老化 / 循環因子 / アミロイドβ / 脳 / 並体結合 / リスク因子 / 加齢 / 老年期認知症 / 先制医療 |
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| Outline of Research at the Start |
老年期認知症の主要な原因であるAlzheimer病の根治的克服には、分子病態をトリガーする脳内Aβ蓄積に対する無症候期の早期介入が不可欠である。脳Aβ蓄積は高齢者の半数近くに認められ、正常老化に伴う軽度の認知機能低下の原因でもあることから、その克服は多くの高齢者のQOL向上につながる。本課題では、モデルマウスの老若並体結合を用い脳Aβ蓄積の加齢依存的循環性リスク因子を同定することから、リスクに関する理解を深め、リスク制御を可能にする方策の開発を目指す。同定する目的因子は、次世代型プレシジョン・メディシンにおいて、認知症リスクへの介入を実現するための標的分子となることが期待できる。
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| Outline of Final Research Achievements |
Alzheimer’s diseases (AD) is the leading cause of senile dementia. Aging is the most important risk factor for AD development. Aggregation and deposition of amyloid-β peptides (Aβ) in brain triggers the pathogenetic process of AD. Aβ levels become abnormal long before onset of severe memory loss, and the strategies to prevent Aβ deposition could have great benefits for effective intervention at the preclinical stage of disease. Our study of heterochronic parabiosis using AD model mice has revealed that circulating factors of younger and older mice can suppress and promote Aβ deposition of model mice through altering the molecular expression profile in brain, respectively. We have successfully identified several molecules of which expression levels in brain were altered by the heterochronic parabiosis. These factors are candidate targets of disease-modifying therapies for AD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により同定した因子は、アルツハイマー病に対するプレクリニカル期からの予防的医療に向けた診断と治療の両面における標的分子として有望であり、短期的には診断手法や創薬リードなどの知的財産を生むことが期待できる。長期的には、プロテイノパシーを基本病態とする脳疾患に対する先制医療の実現が本研究により加速されると予想される。プロテイノパシーは神経変性疾患に限らず、Ⅱ型糖尿病や動脈硬化など加齢に関連する主要疾患の病態でも重要視されており、それらへの効果も期待できる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Extracellular release of ILEI/FAM3C and amyloid-β is associated with the activation of distinct synapse subpopulations.2021
Author(s)
Nakano M, Mitsuishi Y, Liu L, Watanabe N, Hibino E, Hata S, Saito T, Saido C T, Murayama S, Kasuga K, Ikeuchi K, Suzuki T, Nishimura M
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Journal Title
Journal of Alzheimer’s disease
Volume: 80
Issue: 1
Pages: 159-174
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Potential Defense Mechanism Against Amyloid Deposition in Cerebellum2021
Author(s)
Shahnur Alam, Masaki Nakano, Seiko Ishihara, Nobuto Kakuda, Tomohiro Miyasaka, Hina Uchiyama, Yuuna Shirai, Mohammad Moniruzzaman, Takashi Saito, Takaomi C. Saido, Masaki Nishimura, Satoru Funamoto
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 535
Pages: 25-32
DOI
Related Report
Peer Reviewed
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[Journal Article] Generation of transgenic cynomolgus monkeys overexpressing the gene for amyloid-β precursor protein2020
Author(s)
Seita Y, Morimura T, Watanabe N, Iwatani C, Tsuchiya H, Nakamura S, Suzuki T, Yanagisawa D, Tsukiyama T, Nakaya M, Okamura E, Muto M, Ema M, Nishimura M, Tooyama I.
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Journal Title
Journal of Alzheimer's Disease
Volume: -
Issue: 1
Pages: 45-60
DOI
NAID
Related Report
Peer Reviewed / Open Access
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