Three-Dimensional Imaging of Fibrinogen and Neurovascular Alterations in Alzheimer's Disease.
Three-Dimensional Imaging of Fibrinogen and Neurovascular Alterations in Alzheimer's Disease.
复制标题
阿尔茨海默病中纤维蛋白原和神经血管改变的三维成像。
DOI：
10.1007/978-1-0716-2655-9_5
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Akassoglou,Katerina
中科院分区：
文献类型：
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作者：
Merlini,Mario;Sozmen,ElifG;Subramanian,KeshavS;Nana,AlissaL;Seeley,WilliamW;Akassoglou,Katerina
脑血管功能障碍是阿尔茨海默病（AD）的一个标志，与认知能力下降有关。然而，AD中的血脑屏障（BBB）破坏是局灶性的，并且需要灵敏的方法来检测大脑体积中的外渗血蛋白和血管。纤维蛋白原，一种凝血因子，沉积在AD脑中的BBB破坏和脑血管损伤部位。本章介绍了纤维蛋白原免疫标记使能的溶剂清除器官三维（3D）成像（iDISCO）的方法，当与淀粉样蛋白β（Aβ）和血管的免疫标记相结合时，能够灵敏地检测局灶性BBB血管异常，并揭示Aβ斑块和纤维蛋白沉积物在清除人脑大组织体积中的空间分布。总的来说，纤维蛋白原iDISCO能够研究疾病中驱动神经变性的神经血管和神经免疫机制。
Cerebrovascular dysfunction is a hallmark of Alzheimer’s disease (AD) that is linked to cognitive decline. However, blood-brain barrier (BBB) disruption in AD is focal and requires sensitive methods to detect extravasated blood proteins and vasculature in large brain volumes. Fibrinogen, a blood coagulation factor, is deposited in AD brains at sites of BBB disruption and cerebrovascular damage. This chapter presents the methodology of fibrinogen immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs (iDISCO) which, when combined with immunolabeling of amyloid β (Aβ) and vasculature, enables sensitive detection of focal BBB vascular abnormalities, and reveals the spatial distribution of Aβ plaques and fibrin deposits, in large tissue volumes from cleared human brains. Overall, fibrinogen iDISCO enables the investigation of neurovascular and neuroimmune mechanisms driving neurodegeneration in disease.