Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA.
Faraday Energy, Lexington, KY 40511, USA.
Trends Neurosci. 2023 Nov;46(11):901-911. doi: 10.1016/j.tins.2023.08.010. Epub 2023 Sep 28.
Epidemiological evidence demonstrates a link between air pollution exposure and the onset and progression of cognitive impairment and Alzheimer's disease (AD). However, current understanding of the underlying pathophysiological mechanisms is limited. This opinion article examines the hypothesis that air pollution-induced impairment of glymphatic clearance represents a crucial etiological event in the development of AD. Exposure to airborne particulate matter (PM) leads to systemic inflammation and neuroinflammation, increased metal load, respiratory and cardiovascular dysfunction, and sleep abnormalities. All these factors are known to reduce the efficiency of glymphatic clearance. Rescuing glymphatic function by restricting the impact of causative agents, and improving sleep and cardiovascular system health, may increase the efficiency of waste metabolite clearance and subsequently slow the progression of AD. In sum, we introduce air pollution-mediated glymphatic impairment as an important mechanistic factor to be considered when interpreting the etiology and progression of AD as well as its responsiveness to therapeutic interventions.
流行病学证据表明，空气污染暴露与认知障碍和阿尔茨海默病（AD）的发生和进展之间存在关联。然而，目前对于潜在的病理生理机制的理解有限。本文观点认为，空气污染引起的糖质清除功能障碍代表了 AD 发展中的一个关键病因事件。空气中的颗粒物（PM）暴露会导致全身炎症和神经炎症、金属负荷增加、呼吸和心血管功能障碍以及睡眠异常。所有这些因素都已知会降低糖质清除的效率。通过限制致病因素的影响、改善睡眠和心血管系统健康来恢复糖质清除功能，可能会提高废物代谢产物清除的效率，从而减缓 AD 的进展。总之，我们提出了空气污染介导的糖质清除功能障碍作为一个重要的机制因素，在解释 AD 的病因和进展及其对治疗干预的反应时需要加以考虑。
