The prevalence of epilepsy is increased among Alzheimer’s Disease (AD) patients and cognitive impairment is common among people with epilepsy. Epilepsy and AD are linked but the shared pathophysiological changes remain poorly defined. We aim to identify protein differences associated with epilepsy and AD using published proteomics datasets. We observed a highly significant overlap in protein differences in epilepsy and AD: 89% (689/777) of proteins altered in the hippocampus of epilepsy patients were significantly altered in advanced AD. Of the proteins altered in both epilepsy and AD, 340 were altered in the same direction, while 216 proteins were altered in the opposite direction. Synapse and mitochondrial proteins were markedly decreased in epilepsy and AD, suggesting common disease mechanisms. In contrast, ribosome proteins were increased in epilepsy but decreased in AD. Notably, many of the proteins altered in epilepsy interact with tau or are regulated by tau expression. This suggests that tau likely mediates common protein changes in epilepsy and AD. Immunohistochemistry for Aβ and multiple phosphorylated tau species (pTau396/404, pTau217, pTau231) showed a trend for increased intraneuronal pTau217 and pTau231 but no phosphorylated tau aggregates or amyloid plaques in epilepsy hippocampal sections. Our results provide insights into common mechanisms in epilepsy and AD and highlights the potential role of tau in mediating common pathological protein changes in epilepsy and AD.

阿尔茨海默病 (AD) 患者中癫痫的患病率有所增加，并且认知障碍在癫痫患者中很常见。癫痫和 AD 之间存在关联，但共同的病理生理变化仍不清楚。我们的目标是使用已发表的蛋白质组学数据集来识别与癫痫和 AD 相关的蛋白质差异。我们观察到癫痫和 AD 中蛋白质差异高度显着的重叠：癫痫患者海马中 89% (689/777) 改变的蛋白质在晚期 AD 中显着改变。在癫痫和 AD 中发生改变的蛋白质中，有 340 种蛋白质沿相同方向改变，而 216 种蛋白质沿相反方向改变。癫痫和 AD 中突触和线粒体蛋白显着减少，表明常见的疾病机制。相比之下，核糖体蛋白在癫痫症中增加，但在 AD 中减少。值得注意的是，许多在癫痫中发生改变的蛋白质与 tau 相互作用或受 tau 表达调节。这表明 tau 蛋白可能介导癫痫和 AD 中常见的蛋白质变化。Aβ 和多种磷酸化 tau 物种（pTau396/404、pTau217、pTau231）的免疫组织化学显示，癫痫海马切片中神经元内 pTau217 和 pTau231 呈增加趋势，但没有磷酸化 tau 聚集或淀粉样斑块。我们的结果提供了对癫痫和 AD 常见机制的见解，并强调了 tau 在介导癫痫和 AD 常见病理蛋白变化中的潜在作用。