从衰老到阿尔茨海默氏病:一致的大脑DNA甲基化在生命晚期的变化
David Lukacsovich1, Juan I Young2,3, Lissette Gomez3
1Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
medRxiv : the preprint server for health sciences
|June 30, 2025
概括
衰老显著改变大脑中的DNA甲基化 (DNAm),与阿尔茨海默病 (AD) 的变化重叠. 这些表观遗传修饰,特别是在免疫和代谢基因中,可能作为潜在的AD生物标志物.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 神经科学是一个神经科学.
- 老年学是一门学科.
背景情况:
- 老龄化是阿尔茨海默病 (AD) 的主要危险因素.
- 关联衰老与阿尔茨海默氏症的分子机制尚不清楚.
- 基因甲基化 (DNAm) 是一个关键的表观遗传调节器,与衰老和AD有关.
研究的目的:
- 为了识别与人类大脑衰老相关的DNAm差异.
- 为了研究与衰老相关的和AD相关的DNAm变化之间的重叠.
- 探索DNAm作为AD进展的生物标志物的潜力.
主要方法:
- 从ROSMAP和BDR队伍中对死后前额叶皮层中DNAm资料的元分析.
- 血液DNAm数据和全基因组关联研究 (GWAS) 数据的整合.
- 使用阿尔茨海默病神经成像计划 (ADNI) 数据集进行样本外验证.
主要成果:
- 确定了3,264个与年龄相关的CpG,主要是高甲基化和富含基因促进剂.
- 显著的重叠和老化和ADDNAm变化之间的一致方向性.
- 在AZU1促进体中确定了cg10752406作为AD进展的潜在外周生物标志物.
结论:
- 与衰老相关的表观遗传修饰与阿尔茨海默病发病有很强的联系.
- 老龄化中的DNAm变化为AD分子机制提供了洞察力.
- 特定的DNAm位点,如cg10752406,显示为AD的外围生物标志物有前途.
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