2020 Fiscal Year Final Research Report
Development of predictive indicators and treatment strategies for dementia associated with diabetes and obesity focusing TREM2 and monocyte function
| Project/Area Number |
18H02737
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
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Principal Investigator |
Satoh-Asahara Noriko (佐藤哲子) 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究部長 (80373512)
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| Co-Investigator(Kenkyū-buntansha) |
猪原 匡史 国立研究開発法人国立循環器病研究センター, 病院, 部長 (00372590)
二宮 利治 九州大学, 医学研究院, 教授 (30571765)
小谷 和彦 自治医科大学, 医学部, 教授 (60335510)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | TREM2 / 認知症 / 糖尿病 / 肥満 / 早期予知バイオマーカー / 治療戦略 / 単球・ミクログリア |
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| Outline of Final Research Achievements |
The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein mainly expressed on macrophages and microglia, and involved in inflammation. In this study, serum levels of soluble TREM2 (sTREM2) significantly correlated with the decrease of MMSE, a test of cognitive function, in the patients with diabetic enrolled in a National Hospital Organization multicenter study. In the general population of the Hisayama study, incidences of dementia elevated significantly with higher serum sTREM2 levels. These findings suggested that serum sTREM2 levels may be useful to estimate the risk of dementia in clinical practice. Furthermore, we demonstrated that using mice model of dementia, the flavonoid taxifolin, which has strong antioxidant effects, significantly suppress TREM2 expression in hippocampus and amyloid-beta production, resulting in improvement of cognitive function. Accordingly, TREM2 could be an index for predictor and indicator of drug efficacy for dementia.
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| Free Research Field |
肥満、糖尿病、内分泌
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、単球・ミクログリアに特異的に発現し、脳内炎症に関与するTREM2の可溶型sTREM2が日本人一般住民や糖尿病における認知症の予知指標になること、TREM2発現ミクログリアが認知症モデルの病勢を反映して、薬効評価の指標となることを見出した。本研究成果は認知症の効果的な予防戦略の開発に繋がり、超高齢社会が進む本邦において健康寿命延伸や医療費抑制に繋がり、医療と福祉への貢献が期待できる。
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