脑膜动脉网络中的血管粉胺β负载与阿尔茨海默病J20小鼠模型中脑血管血流损失和脑侧血管扩大有关
bioRxiv : the preprint server for biology
|March 31, 2025
概括
阿尔茨海默病在早期就会减少大脑血流 (CBF). 在脑膜动脉上积累的粉样蛋白-β (Aβ) 可能会限制CBF,而扩大的附带血管则试图补偿.
科学领域:
- 神经科学是一个神经科学.
- 脑血管生物学 脑血管生物学
- 阿尔茨海默氏症疾病研究研究
背景情况:
- 全球大脑血流减少 (CBF) 是阿尔茨海默病 (AD) 的早期病理.
- 降低CBF和组织氧化可能导致神经退行.
- 在AD中全球降低CBF的原因尚不清楚.
研究的目的:
- 在阿尔茨海默氏症小鼠模型中,研究粉样β (Aβ) 对神经血管和脑血流 (CBF) 的负担之间的关系.
- 评估Aβ沉积在肝动脉/动脉网中的情况及其对CBF的影响.
- 为了检查补偿性血管机制,以应对Aβ诱导的CBF变化.
主要方法:
- 使用Methoxy-XO4标记粉样β (Aβ) 死亡前.
- 采用了动脉血管标记技术.
- 在年龄较大的WT和J20AD小鼠中评估了Aβ对大脑动脉/动脉网的负担,并测量了大脑血流 (CBF).
主要成果:
- 广泛的血管Aβ负担观察到平动脉/动脉管网络.
- 在J20 AD小鼠中,发现了绕道血液流通系统 - - 皮皮附带动脉小动脉的显著扩大.
- 在12个月大的J20小鼠中,与野生类型的 littermates相比,CBF减少了~15%.
结论:
- 脑膜动脉网络上显著的Aβ负担可能会限制大脑血流 (CBF).
- 扩大的海皮附带血管可能是大脑粉样血管病变 (CAA) 中改变CBF的补偿机制.
- 这些发现突显了血管粉样蛋白在AD病原和CBF调节中的作用.
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