Investigation of key molecules involved in bidirectional interactions between diabetes and dementia

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15272
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: National Center for Geriatrics and Gerontology (2016-2017); Osaka University (2015)
• Principal Investigator: SATO Naoyuki 国立研究開発法人国立長寿医療研究センター, 分子基盤研究部, 部長 (70372612)
• Co-Investigator(Kenkyū-buntansha): 長野 清一 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第五部, 室長 (40362727) ; 竹屋 泰 大阪大学, 医学系研究科, 助教 (70590339)
• Research Collaborator: TAKEYA Miyuki (大西 美幸) ; MUKOUZONO Masahiro
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アルツハイマー病 / 糖尿病 / 遺伝子 / ゲノム編集

Outline of Final Research Achievements

Alzheimer's disease (AD) is one of the major causes of dementia. In addition to APOE4, non-genetic risk factors such as diabetes have also emerged. However, mechanisms by which diabetes increases AD have not been fully understood. To investigate the interactions between AD and diabetes, we generated a novel model with AD and diabetes by crossing amyloid precursor protein (APP) mice and ob/ob mice. These mice show cognitive dysfunction even in young age. We performed gene expression analysis of APP+ob/ob mice. There are genes upregulated only in APP+ob/ob mice. These genes include 37 genes such as Factor X1, a secreted protein, and Factor X2, a transcriptional factor. We are generating gene knockout mice from the genes with the highest changes. Using these knockout mice, we will assess whether these genes could be targets for novel therapeutics for dementia.

Free Research Field

老年医学