A growing body of evidence shows that epileptic activity is frequent but often undiagnosed in patients with Alzheimer's disease (AD) and has major therapeutic implications. Here, we analyzed electroencephalogram (EEG) data from patients with AD and found an EEG signature of transient slowing of the cortical network that we termed paroxysmal slow wave events (PSWEs). The occurrence per minute of the PSWEs was correlated with level of cognitive impairment. Interictal (between seizures) PSWEs were also found in patients with epilepsy, localized to cortical regions displaying blood-brain barrier (BBB) dysfunction, and in three rodent models with BBB pathology: aged mice, young 5x familial AD model, and status epilepticus-induced epilepsy in young rats. To investigate the potential causative role of BBB dysfunction in network modifications underlying PSWEs, we infused the serum protein albumin directly into the cerebral ventricles of naïve young rats. Infusion of albumin, but not artificial cerebrospinal fluid control, resulted in high incidence of PSWEs. Our results identify PSWEs as an EEG manifestation of nonconvulsive seizures in patients with AD and suggest BBB pathology as an underlying mechanism and as a promising therapeutic target.

中文翻译：

---

阿尔茨海默氏病和癫痫发作的阵发性皮层活动缓慢与血脑屏障功能障碍有关。

越来越多的证据表明，癫痫活动在阿尔茨海默氏病（AD）患者中很常见，但常常未被诊断，并且具有重要的治疗意义。在这里，我们分析了AD患者的脑电图（EEG）数据，发现了皮层网络短暂减慢的脑电图特征，我们称其为阵发性慢波事件（PSWEs）。PSWE每分钟的发生与认知障碍的水平相关。在癫痫患者中也发现了发作间隔（发作之间）的PSWE，它们位于显示血脑屏障（BBB）功能障碍的皮质区域，并且在三种具有BBB病理的啮齿动物模型中：老年小鼠，年轻的5x家族性AD模型和癫痫持续状态-诱发年轻大鼠的癫痫病。为了研究BBB功能障碍在PSWEs潜在的网络修饰中的潜在原因，我们将血清蛋白白蛋白直接注入幼稚大鼠的脑室。输注白蛋白而不是人工控制脑脊液，导致PSWE的发生率很高。我们的结果将PSWEs鉴定为AD患者非惊厥性癫痫的一种脑电图表现，并提示BBB病理是一种潜在的机制，也是一种有希望的治疗靶点。