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Abstract：
The brain is a highly vascularized tissue protected by the blood-brain barrier (BBB), a complex structure allowing only necessary substances to pass through into the brain while limiting the entrance of harmful toxins. The BBB comprises several components, and the most prominent features are tight junctions between endothelial cells (ECs), which are further wrapped in a layer of pericytes. Pericytes are multitasked cells embedded in a thick basement membrane (BM) that consists of a fibrous extracellular matrix (ECM) and are surrounded by astrocytic endfeet. The primary function of astrocytes and pericytes is to provide essential blood supply and vital nutrients to the brain. In Alzheimer\'s disease (AD), long-term neuroinflammatory cascades associated with infiltration of harmful neurotoxic proteins may lead to BBB dysfunction and altered ECM components resulting in brain homeostatic imbalance, synaptic damage, and declined cognitive functions. Moreover, BBB structure and functional integrity may be lost due to induced ECM alterations, astrocyte damage, and pericytes dysfunction, leading to amyloid-beta (Aβ) hallmarks deposition in different brain regions. Herein, we highlight how BBB, ECM, astrocytes, and pericytes dysfunction can play a leading role in AD\'s pathogenesis and discuss their impact on brain functions.
摘要：
大脑是受血脑屏障（BBB）保护的高度血管化组织，一种复杂的结构，只允许必要的物质进入大脑，同时限制有害毒素的进入。BBB包括几个组成部分，最突出的特征是内皮细胞（EC）之间的紧密连接，进一步包裹在一层周细胞中。周细胞是嵌入在厚的基底膜（BM）中的多任务细胞，该基底膜由纤维细胞外基质（ECM）组成，并被星形胶质细胞足包围。星形胶质细胞和周细胞的主要功能是为大脑提供必需的血液供应和重要的营养。在阿尔茨海默病（AD）中，与有害神经毒性蛋白浸润相关的长期神经炎症级联反应可能导致BBB功能障碍和ECM成分改变，导致脑稳态失衡。突触损伤,认知功能下降。此外，BBB结构和功能完整性可能由于诱导的ECM改变而丧失，星形胶质细胞损伤，周细胞功能障碍，导致淀粉样β（Aβ）标志沉积在不同的大脑区域。在这里，我们强调了BBB，ECM,星形胶质细胞,周细胞功能障碍在AD的发病机制中起主导作用,并探讨其对脑功能的影响。
