Microvascular Contributions to Alzheimer Disease Pathogenesis: Is Alzheimer Disease Primarily an Endotheliopathy?
Microvascular Contributions to Alzheimer Disease Pathogenesis: Is Alzheimer Disease Primarily an Endotheliopathy?
复制标题
微血管对阿尔茨海默氏病发病机理的贡献：阿尔茨海默氏病主要是内皮病吗？
DOI：
10.3390/biom13050830
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发表时间：
2023-05-13
期刊：
影响因子：
5.5
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中科院分区：
文献类型：
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作者：
阿尔茨海默病（AD）模型基于这样的概念，即异常蛋白质聚集是AD中的主要事件，其在症状发作前十年或更长时间开始，并在神经变性中达到高潮;然而，来自动物和临床研究的新证据表明，由于毛细血管损失和内皮功能障碍导致的血流减少是AD发病机制中的早期和主要事件，其可能先于淀粉样蛋白和tau聚集，并通过直接和间接机制导致神经元和突触损伤。来自临床研究的最新数据表明，内皮功能障碍与AD的认知结果密切相关，并且促进早期AD的内皮修复的治疗策略可能提供预防或减缓疾病进展的潜在机会。本文综述了来自临床、影像学、神经病理学和动物研究的证据，这些证据支持血管对AD病理学的发病和进展的贡献。总之，这些观察结果支持了AD的发病可能主要受血管而不是神经退行性机制影响的观点，并强调了进一步研究AD的血管假说的重要性。
Alzheimer disease (AD) models are based on the notion that abnormal protein aggregation is the primary event in AD, which begins a decade or longer prior to symptom onset, and culminates in neurodegeneration; however, emerging evidence from animal and clinical studies suggests that reduced blood flow due to capillary loss and endothelial dysfunction are early and primary events in AD pathogenesis, which may precede amyloid and tau aggregation, and contribute to neuronal and synaptic injury via direct and indirect mechanisms. Recent data from clinical studies suggests that endothelial dysfunction is closely associated with cognitive outcomes in AD and that therapeutic strategies which promote endothelial repair in early AD may offer a potential opportunity to prevent or slow disease progression. This review examines evidence from clinical, imaging, neuropathological, and animal studies supporting vascular contributions to the onset and progression of AD pathology. Together, these observations support the notion that the onset of AD may be primarily influenced by vascular, rather than neurodegenerative, mechanisms and emphasize the importance of further investigations into the vascular hypothesis of AD.
影响因子：
4
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