Davee Department of Neurology and.
Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
J Clin Invest. 2023 Jul 17;133(14):e171838. doi: 10.1172/JCI171838.
In this issue of the JCI, Wang and colleagues investigate the relationship between sleep disturbances, an environmental risk factor for Alzheimer's disease (AD), and the apolipoprotein 4 (APOEε4) allele, a strong genetic risk factor for AD. The authors subjected an amyloid mouse model expressing human APOE3 or APOE4, with and without human AD-tau injection, to sleep deprivation and observed that amyloid and tau pathologies were worsened in the presence of APOE4. Moreover, decreased microglial clustering and increased dystrophic neurites around plaques were observed in sleep-deprived APOE4 mice. In addition, aquaporin 4, important for clearing amyloid-β through the glymphatic system, was reduced and less polarized to astrocytic endfeet. These APOE4-induced changes caused alterations in sleep behavior during recovery from sleep deprivation, suggesting a feed-forward cycle of sleep disturbance and increased AD pathology that can further disrupt sleep in the presence of APOE4.
在本期 JCI 中，Wang 及其同事研究了睡眠障碍（阿尔茨海默病 (AD) 的环境风险因素）与载脂蛋白 4 (APOEε4) 等位基因（AD 的强烈遗传风险因素）之间的关系。作者使表达人 APOE3 或 APOE4 的淀粉样蛋白小鼠模型接受睡眠剥夺，并观察到在存在 APOE4 的情况下，淀粉样蛋白和 tau 病理学恶化。此外，在睡眠剥夺的 APOE4 小鼠中观察到小胶质细胞聚集减少和斑块周围的神经突变形增加。此外，水通道蛋白 4（对于通过神经淋巴系统清除淀粉样β很重要）减少，并且向星形细胞终足的极化减少。这些 APOE4 引起的变化导致睡眠剥夺后恢复期间睡眠行为的改变，表明睡眠障碍和 AD 病理学增加的正反馈循环，在存在 APOE4 的情况下会进一步破坏睡眠。
