Development of novel evaluation system and prevention strategies for dementia associated with diabetes and obesity focusing on the fat-brain crosstalk and TREM2

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02835
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Department of Clinical Research, National Hospital Organization Kyoto Medical Center
• 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)
• 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)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: TREM2 / 認知症 / 糖尿病 / 肥満 / 脳内炎症 / イメグリミン / タキシフォリン

Outline of Final Research Achievements

We reported in a longitudinal analysis of the NHO multicenter obesity and diabetes cohort that an initially higher sTREM2 level would be a novel predictive marker of cognitive impairment in the non-obese diabetic HbA1c-elevated group. In the dementia/MCI cohort, we also proposed a novel evaluation system for the characteristics and prediction of dementia in T2DM, showing that a decrease in sTREM2 level due to microglial dysfunction could be a starting point for the progress of dementia in the diabetic group. Furthermore, TREM2-knockout mice exhibited that TREM2 could be implicated in glucose metabolism disorders. In addition, taxifolin and imeglimin exhibited anti-inflammatory effects on high-glucose stimulated mouse microglia. In conclusion, our the results are expected the development of effective prevention strategies for dementia in T2DM and contribute to medical care and welfare by extending healthy life expectancy and reducing medical costs in Japan's super-aging society.

Free Research Field

肥満・肥満症、糖尿病、内分泌学

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が非肥満糖尿病患者HbA1cの増悪群における認知機能低下の新規予知指標となること、糖尿病性認知症の発症にはミクログリア機能障害によるsTREM2低下が起点となること、さらに、認知症の発症要因の1つである脳内炎症を糖尿病薬・イメグリミンや植物フラボノイド・タキシフォリンが抑制することを見出した。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。