基础科学和病原发生学
Sally A Frautschy1,2, Kapil Manglani2,3, Xiaohong Zuo1,4
1Veterans Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
在老鼠中,SARS-CoV-2尖端蛋白会加剧阿尔茨海默病 (AD) 病理和补充激活,特别是在高血压或ApoE4存在时. 这突出了在风险人群中长期Covid神经症状的潜在机制.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 持续的症状 (长期Covid) 影响7%的COVID-19幸存者.
- 在SARS-CoV-2中,尖蛋白与ACE2受体结合,从而激活补充通路.
- 长期COVID患者表现出AD生物标志物和神经炎症的升高.
研究的目的:
- 研究高血压和ApoE4对阿尔茨海默病 (AD) 鼠标模型中S1尖端蛋白反应的调节效应.
- 探索蛋白暴露与AD病理,白质损伤和补充激活之间的联系.
主要方法:
- 使用AD和混合AD (AD与大脑小血管疾病) 的老鼠模型,有或没有ApoE4.
- 管理的重组S1蛋白和评估的执行功能,AD病理,白质损伤和补充激活.
- 在大鼠模型和人类神经冠状病毒患者中开发了高通量血测定器,用于血管和中枢神经系统补充激活.
主要成果:
- 不管是ApoE还是高血压,S1蛋白增加了粉样蛋白病理,ptau217和补充激活 (C3,C5b-9).
- 高血压和ApoE4协同作用,恶化尖端诱导的血管病理和白细胞粘附.
- 尖端蛋白诱导执行功能障碍,白质损伤和补体激活,由先前存在的高血压增强.
结论:
- 尖蛋白强烈增加AD病理和补充激活,导致突触损失和血脑屏障损伤,在老鼠与先前存在的AD和血管条件.
- 这些发现与老龄化人口中患有并发症的很大一部分相关.
- 开发可扩展的测试对神经Covid补充激活可以帮助治疗策略.
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