| Project/Area Number |
17H06286
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| Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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| Allocation Type | Single-year Grants |
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| Research Field |
Health science and related fields
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| Research Institution | National Center for Geriatrics and Gerontology |
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Principal Investigator |
Shimada Hiroyuki 国立研究開発法人国立長寿医療研究センター, 老年学・社会科学研究センター, センター長 (00370974)
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| Co-Investigator(Kenkyū-buntansha) |
原田 健次 中京大学, 体育学研究科, 実験実習助手 (70736058)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
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| Keywords | プレクリニカルAD / DNAメチル化 / メチル化 |
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| Outline of Final Research Achievements |
In the present study, we aimed to identify the preclinical AD by amyloid PET imaging and investigate DNA methylation pattern related to amyloid accumulation using genome-wide DNA methylation analysis.
A total of 103 community-dwelling older adults without dementia or neuropsychological diseases were enrolled in this study. According to amyloid PET imaging, 18 (17.5%) individuals were classified as amyloid positive. In the genome-wide DNA methylation analysis of peripheral blood, 2,194 probes were selected as amyloid-related methylation sites. Trough the gene enrichment analysis, several neighboring genes involved in AD or amyloid β were found. These results suggested that DNA methylation could be a useful indicator for screening the preclinical AD.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、ADの治療は、先制医療を実施する必要性があると考えられており、予防薬の開発とともにプレクリニカルADをどのように発見するかが重要な課題となっている。血液サンプルのDNAメチル化からアミロイドの蓄積を予測することが可能となれば、ADの疾病修飾薬開発のレジストリ構築に大きく寄与できる。さらに、本研究の知見を基にプレクリニカルADを高感度に抽出可能なDNAメチル化の解明が進むことで、比較的安価で簡便なスクリーニングが可能となり、広く一般化可能な知見を提示することができる。
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