Karageorgiou Elissaios, Vossel Keith A
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Neurological Institute of Athens, Athens, Greece.
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
Alzheimers Dement. 2017 Sep;13(9):1054-1067. doi: 10.1016/j.jalz.2017.02.003. Epub 2017 Mar 14.
This perspective binds emerging evidence on the bidirectional relationship between Alzheimer's disease (AD) and sleep disorders through a model of brain rhythm attractor breakdown. This approach explains behavioral-cognitive changes in AD across the sleep-wake cycle and supports a causal association between early brainstem tau pathology and subsequent cortical amyloid β accumulation. Specifically, early tau dysregulation within brainstem-hypothalamic nuclei leads to breakdown of sleep-wake attractor networks, with patients displaying an attenuated range of behavioral and electrophysiological activity patterns, a "twilight zone" of constant activity between deep rest and full alertness. This constant cortical activity promotes activity-dependent amyloid β accumulation in brain areas that modulate their activity across sleep-wake states, especially the medial prefrontal cortex. In addition, the accompanying breakdown of hippocampal-medial prefrontal cortex interplay across sleep stages could explain deficient memory consolidation through dysregulation of synaptic plasticity. Clinical implications include the potential therapeutic benefit of attractor consolidation (e.g., slow-wave sleep enhancers) in delaying AD progression.
这种观点通过脑节律吸引子崩溃模型，整合了关于阿尔茨海默病（AD）与睡眠障碍之间双向关系的新证据。这种方法解释了AD患者在睡眠-觉醒周期中的行为认知变化，并支持早期脑干tau蛋白病变与随后皮质淀粉样β蛋白积累之间的因果关联。具体而言，脑干-下丘脑核内早期tau蛋白失调会导致睡眠-觉醒吸引子网络崩溃，患者表现出行为和电生理活动模式范围减弱，在深度休息和完全警觉之间存在持续活动的“模糊地带”。这种持续的皮质活动会促进在睡眠-觉醒状态下调节其活动的脑区，特别是内侧前额叶皮质中依赖活动的淀粉样β蛋白积累。此外，睡眠各阶段海马体-内侧前额叶皮质相互作用的伴随崩溃，可以通过突触可塑性失调来解释记忆巩固不足。临床意义包括吸引子巩固（如慢波睡眠增强剂）在延缓AD进展方面的潜在治疗益处。
