肯塔基大学研究团队发现，阿尔茨海默病患者的睡眠缺失主要源于过度活跃的微胶质细胞（脑免疫细胞），而非淀粉样蛋白斑块本身[1]。研究人员使用药物PLX3397暂时消除了患病小鼠脑内约87%的微胶质细胞，结果显示小鼠每天恢复了超过两小时的睡眠，尽管其脑内淀粉样蛋白斑块的数量未发生变化[1]。这一发现已发表在《阿尔茨海默病与痴呆》期刊上[1]。
研究还揭示了睡眠破坏与斑块积累的相对独立性[1]。在患病小鼠6个月时，早期斑块出现伴随睡眠破坏；但从6个月到18个月，尽管脑内斑块数量翻倍，睡眠问题并未进一步恶化[1]。由香农·麦考利博士和尼古拉斯·康斯坦蒂诺博士领导的这项研究[1]为阿尔茨海默病的治疗开辟了针对微胶质细胞过度活动的新靶点。该项目获得了美国国家衰老研究所、治愈阿尔茨海默病基金会和CART基金的资助支持[1]。
Researchers at the University of Kentucky have identified hyperactive microglia—immune cells in the brain—as the primary driver of sleep loss in Alzheimer's disease, rather than amyloid plaques themselves.[1] Using the drug PLX3397 to temporarily eliminate approximately 87% of microglial cells, diseased mice recovered more than two hours of sleep daily, despite no change in the number of brain amyloid plaques.[1] The findings, published in Alzheimer's & Dementia, suggest a new therapeutic target for addressing sleep disruption in the disease.[1]
The research team, led by Dr. Shannon L. Macauley and Dr. Nicholas J. Constantino, found that early plaque accumulation at six months caused sleep disruption that did not worsen by eighteen months, even as plaque numbers doubled.[1] Dr. Macauley described the discovery as a "paradigm shift," indicating that treatments targeting microglial activation may offer an alternative approach to traditional plaque-clearing strategies.[1] The study was supported by grants from the National Institute on Aging (R01AG068330, R01AG093847, P30AG072946), the Cure Alzheimer's Fund ($287,236), and the CART Fund ($250,000).[1]