在衰老和阿尔茨海默氏病的多模态胆管病理
bioRxiv : the preprint server for biology
|January 9, 2026
概括
胸膜 (ChP) 随着纤维化和化而衰老,在阿尔茨海默氏症 (AD) 中恶化. 巨细胞和纤维细胞功能障碍驱动了衰老和AD中的ChP屏障缺陷.
科学领域:
- 神经科学是一个神经科学.
- 病理学 病理学 病理学
- 衰老研究研究 衰老研究
背景情况:
- 大脑障碍,脑脊液 (CSF) 动态和外围因素与阿尔茨海默病 (AD) 有关.
- 胸膜 (ChP) 是一个关键的血脑接口,产生CSF并形成血-CSF屏障.
- 整个生命周期中ChP病理的发展及其对AD的贡献仍然不充分描述.
研究的目的:
- 系统地描述状 (ChP) 病理在整个寿命和阿尔茨海默氏病 (AD).
- 整合多模式数据,以全面了解CHP功能障碍.
主要方法:
- 多模式地图集49个个体的单核转录学.
- 人工智能辅助的定量组织病理学 >500个死后样本 (16-105岁).
- 在5xFAD小鼠模型中进行空间转录学和功能研究.
主要成果:
- 鉴定了纤维化,化和巨细胞异常作为ChP衰老的标志.
- 观察到的AD病理加剧了ChP的衰老,扩大了亲炎性纤维细胞-巨细胞信号.
- 在5xFAD小鼠中,已证明巨细胞功能障碍会损害上皮质屏障的维护和修复.
结论:
- 建立了一个基础资源,用于研究衰老和AD中的CHP功能障碍.
- 提出了巨细胞-纤维细胞-上皮细胞屏障轴作为ChP病理学的关键驱动因素.
- 突出了ChP在神经退行性疾病发病过程中的作用.
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