Rocca Federica, Kennedy Jaimee, Osman Shamis, Reisz Zita, King Andrew, Bodi Istvan, Al-Sarraj Safa, Troakes Claire
London Neurodegenerative Diseases Brain Bank, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Clinical Neuropathology, King's College Hospital NHS Trust, London, UK.
Neuropathol Appl Neurobiol. 2025 Aug;51(4):e70034. doi: 10.1111/nan.70034.
Evidence suggests Alzheimer's disease (AD) patients are at increased risk of epilepsy and that seizure incidence is associated with faster cognitive decline. Previous studies indicate hyperphosphorylated tau may play a role in this disease association; however, abnormal TDP-43 and α-synuclein deposition have not been extensively examined.
Clinical and neuropathological records of AD cases over a 5-year period were retrieved from the London Neurodegenerative Diseases Brain Bank. The 114 cases were categorised into three groups: AD plus epilepsy, AD plus hippocampal sclerosis (HS) and AD only. Semi-quantitative scores for tau, TDP-43 and α-synuclein pathology within the middle temporal gyrus, hippocampus and amygdala were compared between groups.
A 12% incidence of epilepsy and/or epileptic symptomology was found among the cohort. Twelve cases (11%) showed HS. No significant difference in tau pathology scores was seen between groups. However, a significantly higher score for TDP-43 was seen in AD plus epilepsy compared with AD only in the middle temporal gyrus (p = 0.004). The burden of α-synuclein pathology was increased in the amygdala of AD plus epilepsy and AD plus HS.
The incidence of epilepsy within this AD cohort is higher than expected within the general population (even when matched for age), and this may be associated with increased TDP-43 burden. Understanding the relationship between AD and epilepsy may highlight mechanisms of cellular damage and tissue vulnerability.
有证据表明，阿尔茨海默病（AD）患者患癫痫的风险增加，且癫痫发作发生率与认知功能下降加快有关。既往研究表明，过度磷酸化的tau蛋白可能在这种疾病关联中起作用；然而，异常的TDP-43和α-突触核蛋白沉积尚未得到广泛研究。
从伦敦神经退行性疾病脑库中检索了5年期间AD病例的临床和神经病理学记录。114例病例分为三组：AD合并癫痫、AD合并海马硬化（HS）和单纯AD。比较三组患者颞中回、海马和杏仁核内tau蛋白、TDP-43和α-突触核蛋白病理学的半定量评分。
该队列中癫痫和/或癫痫症状的发生率为12%。12例（11%）表现为HS。各组间tau蛋白病理学评分无显著差异。然而，与单纯AD相比，AD合并癫痫患者颞中回的TDP-43评分显著更高（p = 0.004）。AD合并癫痫和AD合并HS患者杏仁核内α-突触核蛋白病理学负担增加。
该AD队列中癫痫的发生率高于一般人群的预期（即使年龄匹配），这可能与TDP-43负担增加有关。了解AD与癫痫之间的关系可能会揭示细胞损伤和组织易损性的机制。
