Elucidation of the mechanism of behavioral and psychological symptoms in Alzheimer's disease patients using DNA methylation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Jikei University School of Medicine
• Principal Investigator: SHIANGAWA Shunichiro 東京慈恵会医科大学, 医学部, 准教授 (90459628)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: BPSD / 興奮 / 認知症 / アルツハイマー病 / DNAメチル化

Outline of Final Research Achievements

Agitation is the most common and difficult to treat among behavioral and psychological symptoms of dementia (BPSD) . The objective of this study was to identify a region where changes in DNA methylation levels are associated with agitation. Using genome-wide DNA methylation analysis data, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation. The WNT5A DNA methylation level in subjects with agitation was significantly lower than in those without agitation. This change was not influenced by age, sex, body mass index, APOE ε4, medication or inflammatory cytokines. This results suggested an association of agitation with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker of agitation. It may contribute to the elucidation of the mechanism of BPSD.

Free Research Field

老年精神医学

Academic Significance and Societal Importance of the Research Achievements

血液を利用した簡便に実施可能なバイオマーカーが実現すれば、速やかで適正な治療法の選択が可能となる。臨床医の視点に立脚したものとして、患者のQOLの向上と介護負担の軽減に繋がり、社会的な意義は大きい。