生物标志物 生物标志物
Julia Loncke1,2, Cynthia Picard2, Henrik Zetterberg3,4
1Integrated Program in Neuroscience, Faculty of Medicine and Health Science, McGill University, Montréal, QC, Canada.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
补充系统的激活与阿尔茨海默病 (AD) 风险较高的个体的病理和突触变化有关. 这些发现反映了在轻度认知障碍 (MCI) 和AD阶段观察到的模式.
科学领域:
- 神经免疫学 神经免疫学
- 神经退行性疾病 神经退行性疾病
- 阿尔茨海默氏症疾病的发病因子
背景情况:
- 补体系统在突触修剪中发挥作用,但其调节失调与阿尔茨海默氏症 (AD) 病原发生有关.
- 在AD患者中观察到脑脊液 (CSF) 中补充蛋白的升高,但其在症状前和后期阶段的作用尚不清楚.
研究的目的:
- 研究AD家族风险的个体中补充系统蛋白和AD生物标志物之间的关系.
- 探索补充水平与突触完整性和在症状前和症状AD阶段的认知功能的关联.
主要方法:
- 来自PREVENT-AD队列 (家族AD风险) 和ADNI队列 (认知正常,MCI,AD) 的脑脊髓样本被分析为补充蛋白 (C1q,C3,C3b,H因子) 和AD生物标志物 (Aβ42,pTau181,总tau).
- 蛋白质组分析 (SomaScan,OLINK PEA) 和质谱法用于评估补体和突触标记物 (GAP43,SNAP25,SYT1,ADAM22,ADAM23) 的水平.
- 认知功能使用RBANS尺度进行评估.
主要成果:
- 在PREVENT-AD队列中,在tau病理标志物 (pTau181,总tau) 和补充蛋白 (C1q,H因子) 之间发现了显著的积极关联,无论性别和APOE4状态如何.
- 这些补充-tau关联反映了在ADNI队列中的MCI和AD患者中观察到的.
- 补充蛋白C1q和H因子与突触蛋白 (GAP43,SNAP25,SYT1,ADAM23) 有积极的关联,但在PREVENT-AD参与者的认知表现没有.
结论:
- 在具有家族性AD风险的无症状个体中,补体系统激活,病理和突触完整性之间存在明显的联系.
- 风险人群中观察到的补体模式与轻度认知障碍 (MCI) 和AD中发现的类似.
- 为了补充这些发现,正在进行涉及体积核磁共振和PET成像的进一步研究.
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