Sleep Medicine Centre, Department of Systems Medicine, University of Rome 'Tor Vergata", Rome, Italy; Neurology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
Sleep Medicine Centre, Department of Systems Medicine, University of Rome 'Tor Vergata", Rome, Italy.
Mech Ageing Dev. 2021 Mar;194:111434. doi: 10.1016/j.mad.2021.111434. Epub 2021 Jan 11.
The intertwining between epilepsy, sleep disorders and beta amyloid pathology has been progressively highlighted, as early identification and stratification of patients at high risk of cognitive decline is the need of the hour. Modification of the sleep-wake activity, such as sleep impairment or excessive daytime sleepiness, can critically affect cerebral beta amyloid levels. Both mice models and human studies have demonstrated a substantial increase in the burden of beta amyloid pathology after sleep-deprivation, with potential negative effects partially restored by sleep recovery. The accumulation of beta amyloid has been shown to be an early event in the course of Alzheimer's disease dementia. Beta amyloid accumulation has been linked to epileptic seizures epileptic seizures, with beta amyloid being itself pro-epileptogenic in mice models already at oligomeric stage, well before plaque deposition. Further supporting a potential relationship between beta amyloid and epilepsy: i) seizures happen in 1 out of oofut 10 patients with Alzheimer's disease in the prodromal stage, ii) epileptic activity accelerates cognitive decline in Alzheimer's disease, iii) people with late-onset epilepsy present a critically high risk of developing dementia. In this Review we highlight the role of beta amyloid as a potential shared mechanisms between sleep disorders, late-onset epilepsy, and cognitive decline.
癫痫、睡眠障碍和β淀粉样蛋白病理学之间的相互关系逐渐得到强调，因为早期识别和分层高认知衰退风险的患者是当务之急。睡眠-觉醒活动的改变，如睡眠障碍或日间嗜睡，会严重影响大脑β淀粉样蛋白水平。小鼠模型和人类研究都表明，睡眠剥夺后β淀粉样蛋白病理学负担会显著增加，而睡眠恢复可以部分恢复潜在的负面影响。β淀粉样蛋白的积累已被证明是阿尔茨海默病痴呆症病程中的早期事件。β淀粉样蛋白的积累与癫痫发作有关，β淀粉样蛋白在寡聚体阶段已经在小鼠模型中具有致癫痫作用，远早于斑块沉积之前。进一步支持β淀粉样蛋白和癫痫之间存在潜在关系：i）在前驱期，阿尔茨海默病患者中有 1 分之一会发生癫痫发作，ii）癫痫活动会加速阿尔茨海默病的认知衰退，iii）迟发性癫痫患者发生痴呆的风险极高。在这篇综述中，我们强调了β淀粉样蛋白作为睡眠障碍、迟发性癫痫和认知衰退之间潜在共同机制的作用。
