基础科学和病原发生学
Jorge Garcia Condado1,2,3, Colin Birkenbihl1, Hannah M Klinger1
1Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
对加速灰质大脑衰老的遗传倾向与p-tau217升高有关,这是阿尔茨海默病早期生物标志物,特别是在老年人中. 这突显了AD病变发生过程中与年龄相互作用的遗传易感性.
科学领域:
- 神经成像和遗传学
- 生物标志物研究 生物标志物研究
- 阿尔茨海默氏症疾病的发病因子
背景情况:
- 大脑年龄差距通过神经成像量化大脑年龄差异.
- 脑年龄差异的多基因风险评分 (PRS) 估计了对加速大脑衰老的遗传倾向.
- 了解遗传性大脑衰老倾向与早期阿尔茨海默病 (AD) 生物标志物之间的联系对于早期检测和干预至关重要.
研究的目的:
- 研究更高或更低BrainAge Gap的遗传倾向与AD的血生物标志物之间的关联.
- 探索影响大脑衰老的遗传因素如何与早期AD相关的变化有关.
- 提高对早期AD机制和风险因素的理解.
主要方法:
- 来自A4和LEARN研究的3014名认知正常参与者的分析.
- 对灰色物质 (GM),白色物质 (WM) 和功能连接 (FC) BrainAge模型的PRS计算.
- 血生物标志物的评估:p-tau217,GFAP和NfL,使用一般线性模型与年龄和PRS的相互作用术语.
主要成果:
- 基于Aβ-PET状态,APOEε4载体,年龄,性别或教育,BrainAge PRS没有显著差异.
- BrainAge GM PRS显示了与p-tau217水平 (p=0.01) 的积极关联,特别是在老年人中 (p=0.007).
- 在任何BrainAge PRS和GFAP或NfL水平之间没有发现显著的关联.
结论:
- 促进加速灰质大脑衰老的遗传因素与p-tau217有关,这是一个敏感的AD标志物.
- 这种遗传倾向在老年人中更为明显,表明与年龄相关的相互作用.
- 与灰色物质BrainAge PRS的特定关联表明它有可能成为AD风险的早期标志物.
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