Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO 63110, USA.
The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Int J Mol Sci. 2024 Sep 23;25(18):10228. doi: 10.3390/ijms251810228.
Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder characterized by recurrent focal seizures originating in the temporal lobe. Despite the variety of antiseizure drugs currently available to treat TLE, about 30% of cases continue to have seizures. The etiology of TLE is complex and multifactorial. Increasing evidence indicates that Alzheimer's disease (AD) and drug-resistant TLE present common pathological features that may induce hyperexcitability, especially aberrant hyperphosphorylation of tau protein. Genetic polymorphic variants located in genes of the microtubule-associated protein tau () and glycogen synthase kinase-3β () have been associated with the risk of developing AD. The allele is a major genetic risk factor for AD. Likewise, a gene-dose-dependent effect of seems to influence TLE. The present study aimed to investigate whether the allele and genetic variants located in the and genes are associated with the risk of developing AD and drug-resistant TLE in a cohort of the Mexican population. A significant association with the allele was observed in patients with AD and TLE. Additional genetic interactions were identified between this allele and variants of the and genes.
颞叶癫痫(TLE)是一种慢性神经系统疾病,其特征是起源于颞叶的复发性局灶性癫痫发作。尽管目前有多种抗癫痫药物可用于治疗 TLE,但约 30%的病例仍有发作。TLE 的病因复杂且多因素。越来越多的证据表明,阿尔茨海默病(AD)和耐药性 TLE 具有共同的病理特征,可能导致过度兴奋,特别是tau 蛋白的异常过度磷酸化。位于微管相关蛋白 tau()和糖原合成酶激酶-3β()基因中的遗传多态性变体与发生 AD 的风险相关。等位基因是 AD 的主要遗传危险因素。同样,似乎 基因剂量依赖性影响 TLE。本研究旨在调查位于和基因中的 等位基因和遗传变异是否与墨西哥人群队列中 AD 和耐药性 TLE 的发病风险相关。在 AD 和 TLE 患者中观察到与等位基因显著相关。此外,还确定了该等位基因与和基因变异之间的其他遗传相互作用。