Khandayataray Pratima, Murthy Meesala Krishna
Department of Biotechnology, Academy of Management and Information Technology, Utkal University, Bhubaneswar, Odisha 752057, India.
Department of Allied Health Sciences, Chitkara School of Health Sciences, Chitkara University, Punjab 140401, India.
Neuroscience. 2025 May 14;574:21-41. doi: 10.1016/j.neuroscience.2025.03.066. Epub 2025 Apr 4.
We reviewed the connections among Alzheimer's disease (AD), sleep deprivation, and circadian rhythm disorders. Evidence is mounting that disrupted sleep and abnormal circadian rhythms are not merely symptoms of AD, but are also involved in accelerating the disease. Amyloid-beta (Aβ) accumulates, a feature of AD, and worsens with sleep deprivation because glymphatic withdrawal is required to clear toxic proteins from the brain. In addition, disturbances in circadian rhythm can contribute to the induction of neuroinflammation and oxidative stress, thereby accelerating neurodegenerative processes. While these interactions are bidirectional, Alzheimer's pathology further disrupts sleep and circadian function in a vicious cycle that worsens cognitive decline, which is emphasized in the review. The evidence that targeting sleep and circadian mechanisms may serve as therapeutic strategies for AD was strengthened by this study through the analysis of the molecular and physiological pathways. Further work on this nexus could help unravel the neurobiological mechanisms common to the onset of Alzheimer's and disrupted sleep and circadian regulation, which could result in earlier intervention to slow or prevent the onset of the disease.
我们回顾了阿尔茨海默病（AD）、睡眠剥夺和昼夜节律紊乱之间的联系。越来越多的证据表明，睡眠中断和异常的昼夜节律不仅是AD的症状，还参与加速疾病进程。β-淀粉样蛋白（Aβ）会积累，这是AD的一个特征，且会因睡眠剥夺而加剧，因为清除大脑中有毒蛋白质需要脑脊液流出减少。此外，昼夜节律紊乱会导致神经炎症和氧化应激的诱导，从而加速神经退行性过程。虽然这些相互作用是双向的，但阿尔茨海默病病理会进一步扰乱睡眠和昼夜节律功能，形成恶性循环，加剧认知衰退，本综述强调了这一点。通过对分子和生理途径的分析，该研究加强了针对睡眠和昼夜节律机制可能作为AD治疗策略的证据。关于这一联系的进一步研究可能有助于揭示阿尔茨海默病发病以及睡眠和昼夜节律调节紊乱所共有的神经生物学机制，这可能会带来更早的干预措施，以减缓或预防疾病的发生。
