Elucidation of Alzheimer disease pathology in obesity focus on association between brain and other organs and lipid metabolism in glial cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20569
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0601:Agricultural chemistry and related fields
• Research Institution: Nagoya University
• Principal Investigator: Kawade Noe 名古屋大学, 環境医学研究所, 特任助教 (20910574)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: アルツハイマー病 / グリア細胞 / 肥満 / 脂質代謝 / 脳・全身連関

Outline of Final Research Achievements

In this study, we showed alterations of brain lipid profile and gene expressions in oligodendrocyte (produces myelin) related to lipid metabolism in AD mice. These results suggested that lipid metabolism in oligodendrocyte is changed in brain with AD pathology. On the other hands, relationship between brain lipid metabolism and oligodendrocyte abnormality were not confirmed. Moreover, effects of high fat diet intake on AD pathologies were not detected in this study. Alteration of hepatic cholesterol level and blood profile were observed in AD mice, which suggested that abnormalities in organs except brain affect AD pathologies.

Free Research Field

病態神経科学

Academic Significance and Societal Importance of the Research Achievements

脂質代謝に関わる遺伝子や代謝性疾患がアルツハイマー病（AD）のリスク因子として知られていることから、ADの脳では脂質代謝が変動していると推察されたが、その詳細な機構は不明な部分が多い。本研究では、その細胞組成の大半が脂質で占められるオリゴデンドロサイトに着目し、リピドーム解析も交えて、ADと脳の脂質代謝に関する新たな知見を得た。また、近年、AD発症・増悪には脳以外の組織が関与することが指摘されており、本研究では脳と代謝組織の連関を明らかにする手がかりを得た。