Wang Niya, Yang Xiang, Zhao Zhong, Liu Da, Wang Xiaoyan, Tang Hao, Zhong Chuyu, Chen Xinzhang, Chen Wenli, Meng Qiang
Department of Neurology, The First People's Hospital of Yunnan Province, Kunming, China.
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Front Mol Neurosci. 2023 Aug 16;16:1227493. doi: 10.3389/fnmol.2023.1227493. eCollection 2023.
The amyloid-β (Aβ) hypothesis was once believed to represent the pathogenic process of Alzheimer's disease (AD). However, with the failure of clinical drug development and the increasing understanding of the disease, the Aβ hypothesis has been challenged. Numerous recent investigations have demonstrated that the vascular system plays a significant role in the course of AD, with vascular damage occurring prior to the deposition of Aβ and neurofibrillary tangles (NFTs). The question of how Aβ relates to neurovascular function and which is the trigger for AD has recently come into sharp focus. In this review, we outline the various vascular dysfunctions associated with AD, including changes in vascular hemodynamics, vascular cell function, vascular coverage, and blood-brain barrier (BBB) permeability. We reviewed the most recent findings about the complicated Aβ-neurovascular unit (NVU) interaction and highlighted its vital importance to understanding disease pathophysiology. Vascular defects may lead to Aβ deposition, neurotoxicity, glial cell activation, and metabolic dysfunction; In contrast, Aβ and oxidative stress can aggravate vascular damage, forming a vicious cycle loop.
淀粉样β（Aβ）假说曾被认为代表了阿尔茨海默病（AD）的致病过程。然而，随着临床药物研发的失败以及对该疾病认识的不断加深，Aβ假说受到了挑战。最近大量研究表明，血管系统在AD病程中起着重要作用，血管损伤发生在Aβ沉积和神经原纤维缠结（NFTs）之前。Aβ如何与神经血管功能相关以及AD的触发因素是什么这一问题最近成为了焦点。在这篇综述中，我们概述了与AD相关的各种血管功能障碍，包括血管血流动力学、血管细胞功能、血管覆盖以及血脑屏障（BBB）通透性的变化。我们回顾了关于复杂的Aβ - 神经血管单元（NVU）相互作用的最新发现，并强调了其对于理解疾病病理生理学的至关重要性。血管缺陷可能导致Aβ沉积、神经毒性、神经胶质细胞活化和代谢功能障碍；相反，Aβ和氧化应激会加重血管损伤，形成恶性循环。
