生物标志物 生物标志物
Shannon M Drouin1, Pei-Lun Kuo2, Cassandra O Blew1
1Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 26, 2025
概括
表观遗传标记,如DNA甲基化 (DNAm) 测量,提供对蛋白质水平的稳定见解,将其与大脑衰老和认知衰退联系起来. 这项研究发现特定的DNAm EpiScores与神经退行和认知轨迹密切相关.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 老年学是指老年学的学科.
背景情况:
- 血蛋白质组与老化大脑和认知的关联是有信息的,但受蛋白质变异性和测量错误的限制.
- 表观遗传措施,特别是DNA甲基化 (DNAm),可能为蛋白质丰富提供更稳定的代理.
- 基于DNAm的蛋白质代理可以提供更强大的与大脑衰老和神经退行相关联.
研究的目的:
- 研究基于蛋白质的表观遗传分数 (EpiScores) 与纵向大脑结构和衰老中的认知轨迹的关联.
- 为了确定DNAm蛋白质丰度的测量是否比血蛋白质水平更强烈地与神经退行性结果相关.
主要方法:
- 利用了来自巴尔的摩长度衰老研究的认知正常老年人的纵向DNAm数据 (n=431-681).
- 应用潜增长曲线模型,将109个基于蛋白质的EpiScores与大脑总体体积,阿尔茨海默病易受伤害的大脑区域 (SPARE-AD),高级大脑衰老 (SPARE-BA) 和认知的轨迹联系起来.
- 包括多达8次访问和超过16年的随访神经成像和认知数据.
主要成果:
- 十个EpiScore显示出与至少一个结果的显著关联 (p < 0.00001).
- 特定的EpiScores (B2 微球蛋白,斯坦尼奥卡尔.1,奇托里奥酶.1,溶酶,PARC) 与增加的SPARE-AD相关.
- EpiScore MMP12与大脑总体体积和认知能力的下降,以及SPARE-AD的增加有关.
- 血MMP12EpiScore解释了22%的血MMP12变异,并与677种其他血蛋白相关联,这表明它涉及炎症和信号通路.
结论:
- 循环蛋白丰富性的表观遗传指标,如MMP12的DNAm测量,与认知衰老密切相关.
- 这些表观遗传标记也与MRI定义的神经退行性轨迹有关.
- 基于DNAm的蛋白质代理代表了理解和潜在地减轻与年龄相关的大脑变化的有希望的途径.
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