Peripheral Pathways to Neurovascular Unit Dysfunction, Cognitive Impairment, and Alzheimer's Disease.
Peripheral Pathways to Neurovascular Unit Dysfunction, Cognitive Impairment, and Alzheimer's Disease.
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DOI：
10.3389/fnagi.2022.858429
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发表时间：
2022
影响因子：
4.8
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中科院分区：
文献类型：
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阿尔茨海默病(AD)是痴呆症最常见的形式。它在一个多世纪前首次被描述，科学家们每天都在获取关于这种疾病的新数据和新信息。尽管仍有一些细微差别和细节在不断揭开，但奥斯卡·费舍尔博士和阿洛伊斯·阿尔茨海默博士在1900年初的《S》中发现了许多关键因素，包括淀粉样β蛋白(Aβ)、tau蛋白、血管异常、胶质细胞增生以及感染的可能作用。最近，人们对神经血管单位功能障碍越来越感兴趣和重视，这种功能障碍发生在轻度认知损害之前，并且独立于Aβ和tau脑积聚。在过去的十年里，有证据表明，Aβ和tau寡聚体是在对感染做出反应时产生的抗菌肽，这扩大了我们的知识，并挑战了先入为主的观念。病原体引起的感染产生与偶发痴呆相关的先天性免疫反应(例如，外周器官产生的β和tau)的概念值得在根本原因未知的散发性AD的背景下考虑。因此，提出外周淀粉样蛋白假说与认知功能障碍和阿尔茨海默病的关系尚待进一步研究验证。与此同时，人类仍然是复杂的可变有机体，具有定义其免疫状态、神经血管功能和神经元可塑性的个人风险因素。在这篇重点综述中，将探讨和讨论感染和器官功能障碍通过周围淀粉样蛋白和/或神经血管单位功能障碍的产生而导致阿尔茨海默病的想法。归根结底，许多问题仍有待回答，并强调了未来探索的关键领域。
Alzheimer’s disease (AD) is the most common form of dementia. It was first described more than a century ago, and scientists are acquiring new data and learning novel information about the disease every day. Although there are nuances and details continuously being unraveled, many key players were identified in the early 1900’s by Dr. Oskar Fischer and Dr. Alois Alzheimer, including amyloid-beta (Aβ), tau, vascular abnormalities, gliosis, and a possible role of infections. More recently, there has been growing interest in and appreciation for neurovascular unit dysfunction that occurs early in mild cognitive impairment (MCI) before and independent of Aβ and tau brain accumulation. In the last decade, evidence that Aβ and tau oligomers are antimicrobial peptides generated in response to infection has expanded our knowledge and challenged preconceived notions. The concept that pathogenic germs cause infections generating an innate immune response (e.g., Aβ and tau produced by peripheral organs) that is associated with incident dementia is worthwhile considering in the context of sporadic AD with an unknown root cause. Therefore, the peripheral amyloid hypothesis to cognitive impairment and AD is proposed and remains to be vetted by future research. Meanwhile, humans remain complex variable organisms with individual risk factors that define their immune status, neurovascular function, and neuronal plasticity. In this focused review, the idea that infections and organ dysfunction contribute to Alzheimer’s disease, through the generation of peripheral amyloids and/or neurovascular unit dysfunction will be explored and discussed. Ultimately, many questions remain to be answered and critical areas of future exploration are highlighted.