Roles of neural metabolic signaling pathway in transitional mechanism to AD

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H02188
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: Akiko Taguchi 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 部長 (80517186)
• Co-Investigator(Kenkyū-buntansha): 福井 裕介 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 研究員 (60824802) ; 田之頭 大輔 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 研究員 (80724575) ; 王 蔚 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 研究員 (00845167)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 糖尿病 / 糖代謝調節 / 脳 / 認知機能 / 加齢 / 糖代謝調節経路 / アルツハイマー病

Outline of Final Research Achievements

We found that1) type2 diabetes (T2DM)-induced memory decline accompanied by alterations in glucose metabolism-related signaling components in the hippocampus is provoked by an amyloid beta (Aβ)-independent mechanism, 2) type1 diabetes (T1DM)-induced memory deficit arises independently of the modification of glucose metabolism-related signaling factors and independently of Aβ, 3) hippocampal alterations in glucose metabolism-related signaling occur when middle-aged novel AD model mice show cognitive decline, 4) T2DM additively exacerbates cognitive impairment and alterations in hippocampal glucose metabolism-related signaling in middle-aged novel AD model mice, and 5) aged mice that have normal glucose metabolism display Aβ-unrelated memory impairment accompanied by alterations in hippocampal glucose metabolism-related signaling as well as T2DM model mice show.

Free Research Field

神経内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、脳の糖代謝調節経路とAβ非依存的認知機能低下の関係および同経路とAβの関係を明らかにした点で学術的意義が深い。これらの詳細なメカニズムについての今後の検討により、認知機能障害の新たな予防・治療法の開発に貢献する可能性がある。