线粒体DNA拷贝数与人体突变和脆弱性相关的痴呆风险有关
Qu Tian1, David A Zweibaum2, Yong Qian2
1Translational Gerontology Branch, National Institute on Aging Intramural Research Program, 251 Bayview Blvd., Suite 100, Baltimore, MD, 21224, USA. qu.tian@nih.gov.
GeroScience
|September 23, 2024
概括
血液中较高的线粒体DNA拷贝数 (mtDNAcn) 与降低痴呆风险有关,特别是非阿尔茨海默氏症痴呆. 这种关联在脆弱或高体质突变的个体中更为强烈.
科学领域:
- 遗传学 是一个遗传学.
- 神经学 神经学
- 衰老的衰老 衰老的衰老
背景情况:
- 线粒体功能障碍与身体障碍和痴呆症有关.
- 血液线粒体DNA拷贝数 (mtDNAcn) 可能预测认知能力下降,但体突变和虚弱的影响仍然不清楚.
研究的目的:
- 调查血液mtDNAcn与随后的痴呆风险之间的关联.
- 检查mtDNAcn与认知功能之间的关系,考虑到脆弱性和微型异质体.
主要方法:
- 来自189566名参与者的全基因组测序 (WGS) 数据被用于估计mtDNAcn和microheteroplasmies.
- 考克斯回归模型评估了mtDNAcn与痴呆症诊断之间的关联,在13.2年的随访期间进行了随访.
- 多变量线性回归分析了与mtDNAcn相关的认知指标,根据共变量进行调整,并按脆弱性和微heteroplasmies进行分层.
主要成果:
- 每个mtDNAcn标准偏差的增加都与4.2%更低的全因痴呆风险和6%更低的非阿尔茨海默氏症痴呆风险有关.
- 这些关联在易受伤害,易受伤害或具有较高水平的微heteroplasmies的个体中更为明显.
- 较高的mtDNAcn与数字符号替换测试 (DSST) 的更好表现相关,并且在具有较高微heteroplasmies或脆弱性的人群中显著.
结论:
- 通过WGS确定血液mtDNAcn的增加与痴呆的风险降低有关,特别是非阿尔茨海默氏症痴呆.
- mtDNAcn对痴呆风险和认知功能的保护作用似乎在具有较高体质突变或脆弱性的个体中得到放大.
- 需要进一步的研究来阐明连接mtDNAcn,脆弱性,身体突变和痴呆的潜在生物机制.
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