睡眠障碍对阿尔茨海默病影响的研究进展

Research Progress on the Impact of Sleep Disorders on Alzheimer’s Disease

摘要: 认识和了解阿尔茨海默病(Alzheimer’s disease, AD)以及它与睡眠之间的关系。本文采用文献分析的方法。AD是一种以进行性认知功能障碍和行为障碍为特征，发生在老年和老年早期的中枢神经退行性疾病，其神经病理学特征为Aβ聚集的细胞外老年斑块，以及由高磷酸化tau蛋白聚集的细胞内神经原纤维缠结的形成。因此为预防AD就要避免Aβ在脑内堆积形成斑块，清除Aβ就尤其重要了。Aβ的清除主要通过淋巴系统。在淋巴途径中，脑实质内间质液(Interstitial fluid, ISF)通过静脉周围外流平衡脑脊液(cerebrospinal fluid, CSF)的对流内流，使神经泌液清除掉包括Aβ在内的有毒性蛋白代谢物。脑内淋巴系统的清除工作在夜间更为活跃。剥夺一个晚上的睡眠时间会导致海马，海马旁和丘脑区域的Aβ水平明显升高。由此可见，睡眠障碍可能导致AD的部分原因是促进大脑中Aβ的积累。睡眠不足，会导致Aβ来不及运走，在脑内堆积形成斑块，尤其是在产生深睡眠的区域，会影响并损害这些区域。由于这种损害从而减少了深睡眠时间，又反过来减低了夜间清除这些代谢废物的能力，导致更多的Aβ堆积。大脑中Aβ负荷的增加与脑功能的损害有关。防止大脑中Aβ积累的方式可以促进大脑健康衰老，并有助于预防AD。因此保证充足的睡眠时间以及提高睡眠质量能有效的降低脑内Aβ的水平，进而降低患AD的风险。

Abstract: To recognize and understand the relationship between Alzheimer’s disease (AD) and sleep, this paper adopts the method of literature analysis. AD is a central neurodegenerative disease charac- terized by progressive cognitive dysfunction and behavioral disorders in old age and early old age. Its neuropathology is characterized by the accumulation of extracellular senile plaques with Aβ and the formation of intracellular neurofibrillary tangles with highly phosphorylated tau. Therefore, in order to prevent AD, it is necessary to avoid the accumulation of Aβ in the brain to form plaques, and the removal of Aβ is particularly important. Aβ is cleared mainly through the lymphatic system. In the lymphatic pathway, Interstitial fluid (ISF) in the brain parenchyma balances the convective influx of cerebrospinal fluid (CSF) through perivenous efflux, which clears the neurosecretion of toxic protein metabolites, including Aβ. Clearance of the lymphatic system in the brain is more ac-tive at night. One night of sleep deprivation leads to a marked increase in Aβ levels in the hippo-campus, par hippocampal and thalamic regions. It follows that sleep disorders may contribute to AD in part by promoting Aβ accumulation in the brain. When you don’t get enough sleep, Aβ doesn’t travel fast enough to build up plaques in the brain, especially in areas that produce deep sleep, af-fecting and damaging those areas. This damage reduces the amount of deep sleep, which in turn reduces the ability to clear these metabolic wastes at night, leading to more Aβ accumulation. In-creased Aβ load in the brain is associated with impaired brain function, preventing Aβ accumula-tion in the brain in a way that promotes healthy brain aging and helps prevent AD. Therefore, en-suring adequate sleep time and improving sleep quality can effectively reduce the level of Aβ in the brain, and then reduce the risk of AD.