Towards therapeutic modulation of amyloid beta clearance from the brain during sleep

越来越多的证据表明，健康人群多年反复出现的睡眠障碍可能触发或加速导致痴呆的病理过程，例如引起氧化应激或增强淀粉样蛋白沉积。该项目将探讨睡眠如何影响阿尔茨海默病的神经病理学的开始和进展。我们特别感兴趣的是了解导致高危人群发病的最早事件。这项工作将集中在以下问题上：在非快速眼动睡眠中，可溶性淀粉样蛋白水平通过什么机制降低？长期睡眠不足是否会阻碍小胶质细胞的反应或降低它们处理淀粉样斑块的能力？

Evidence is building that sleep disturbances in healthy people, repeated over years, might trigger or accelerate pathological processes leading to dementia, e.g. by causing oxidative stress or enhancing amyloid deposition. The project will address how sleep influences the initiation and progression of the neuropathology of Alzheimer's disease. We are interested particularly in understanding the earliest events responsible for driving the onset of disease pathology in people at risk. The work will focus on questions such as: By what mechanism(s) do soluble amyloid levels decrease in NREM sleep? Does chronic sleep deprivation hinder microglia responses or down regulate their ability to tackle amyloid plaques?