Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.

Amyloid-β (Aβ) accumulation in the brain extracellular space is a hallmark of Alzheimer’s disease (AD). The factors regulating this process are only partly understood. Aβ aggregation is a concentration-dependent process that is likely to be dependent on changes in brain interstitial fluid (ISF) levels of Aβ. Using in vivo microdialysis, we found that ISF Aβ levels correlated with wakefulness. ISF Aβ levels also significantly increased during acute sleep deprivation and during orexin infusion, whereas they decreased with infusion of a dual orexin receptor antagonist. Importantly, chronic sleep restriction significantly increased and a dual orexin receptor antagonist decreased Aβ plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of AD.

β - 淀粉样蛋白（Aβ）在大脑细胞外间隙的积聚是阿尔茨海默病（AD）的一个标志性特征。对调节这一过程的因素仅有部分了解。Aβ聚集是一个浓度依赖性过程，很可能取决于大脑间质液（ISF）中Aβ水平的变化。通过体内微透析，我们发现ISF中的Aβ水平与觉醒状态相关。在急性睡眠剥夺期间以及食欲素输注期间，ISF中的Aβ水平也显著升高，而在输注双重食欲素受体拮抗剂时则降低。重要的是，在淀粉样前体蛋白转基因小鼠中，慢性睡眠限制显著增加了Aβ斑块的形成，而双重食欲素受体拮抗剂则减少了Aβ斑块的形成。因此，睡眠 - 觉醒周期和食欲素可能在AD的发病机制中起作用。