Analysis of methylation of APP gene in Alzheimer's disease and Down syndrome

• Project/Area Number: 16K19770
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Ehime University
• Principal Investigator: Mori Yoko 愛媛大学, 医学部附属病院, 助教 (30646245)
• Research Collaborator: Onishi Chiemi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アルツハイマー病 / ダウン症候群 / メチル化解析 / 遺伝子発現 / APP遺伝子 / DNAメチル化 / エピジェネティクス / 遺伝子メチル化 / 遺伝子 / 発現制御 / 脳神経疾患

Outline of Final Research Achievements

Alzheimer’s disease (AD) is known as the most frequent causes of degenerative dementia that is produced by the abnormal accumulation of beta amyloid (Aβ). Aβ derives from amyloid precursor protein (APP) that is one of the responsible gene for familial AD. Down syndrome (DS) is caused by triplication of chromosome 21 which includes APP gene (21q21). In DS, the cognitive decline occurs in early 40s caused by similarly pathology with AD. In this study, we analyzed the DNA methylation rate at 27 CpG site in APP promoter region in AD patients and DS patients compared to each control subjects. Genomic DNA from peripheral leukocytes was analyzed. In DS, the methylation rate was significantly higher than control subjects and was tend to increase with advancing age. In AD patients the methylation rate was higher in severe cognitive dysfunction group than mild dysfunction group.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病は現在65歳以上の5人に1人が認知症と言われる我が国において早期診断を確実に行うことが求められている疾患の一つである。本研究では末梢血を用いてアルツハイマー病とダウン症候群患者でのAPP遺伝子のメチル化割合を解析することでその発現調節機構の一端を解明し、脳内でアミロイドβが蓄積されつつある段階で末梢血でAPP遺伝子のメチル化割合の解析を行うことが早期診断につながる可能性について検討した