基础科学和病原发生学
Isabel MacKenzie Sarty1, Cynthia Picard1, Henrik Zetterberg2,3
1Douglas Mental Health University Institute, Montreal, QC, Canada.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
介素-18 (IL-18) 信号传递与衰老和阿尔茨海默病 (AD) 的进展有关,主要影响病理和突触损伤. 这一途径影响认知,并可能解释TAU,突触衰退和AD认知障碍之间的联系.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 老年学是指老年学的学科.
背景情况:
- 炎症在阿尔茨海默氏症 (AD) 中起着复杂的作用,可能会防止早期的粉样蛋白沉积,但稍后会恶化病理.
- 与年龄相关的慢性炎症 (炎症) 中的关键因素NLRP3炎症酶与AD有关.
- 作为NLRP3激活的标记物,介质素-18 (IL-18) 在整个AD连续性中被研究其作用.
研究的目的:
- 探索IL-18信号级联在阿尔茨海默氏症 (AD) 病原发生中的作用.
- 研究IL-18与衰老的关联,阿尔茨海默病理 (陶和粉胺β),突触损伤和认知功能.
- 用纵向和横截面数据检查在症状前和症状AD阶段的IL-18.
主要方法:
- 利用了来自PREVENT-AD队列 (风险/预症状AD) 的纵向数据和来自ADNI队列 (症状AD和认知无损) 的横截面数据.
- 分析了脑脊液 (CSF) 和死后大脑组织的IL-18级联蛋白,AD病理标志物 (tau,Aβ42),突触损伤标志物和认知评分.
- 采用一般和混合线性模型,ELISA,ECLIA,OLINK测定和质谱分析.
主要成果:
- 脑流中的IL-18水平和脑组织中的IL-18mRNA随着年龄的增长而增加.
- IL-18信号蛋白与CSF和大脑组织中病态增加有显著的关联.
- 一个IL-1受体基因集群中的遗传变异与tau病理相关.
- IL-18信号与预症状AD队列中的认知功能和突触标志物水平有关.
结论:
- 根据年龄调节IL-18信号级联,在阿尔茨海默病的症状前阶段发挥重要作用.
- IL-18信号主要影响AD连续性的tau病理,对粉样β病理的影响最小.
- 这些发现可能会阐明TAU病理,突触退化和AD的认知衰退之间的关系.
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