Synergistic Effect between the APOE ε4 Allele with Genetic Variants of GSK3B and MAPT: Differential Profile between Refractory Epilepsy and Alzheimer Disease

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 (<i>MAPT</i>) and glycogen synthase kinase-3β (<i>GSK3B</i>) have been associated with the risk of developing AD. The <i>APOE ε4</i> allele is a major genetic risk factor for AD. Likewise, a gene-dose-dependent effect of <i>ε4</i> seems to influence TLE. The present study aimed to investigate whether the <i>APOE ɛ4</i> allele and genetic variants located in the <i>MAPT</i> and <i>GSK3B</i> 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 <i>APOE ε4</i> allele was observed in patients with AD and TLE. Additional genetic interactions were identified between this allele and variants of the <i>MAPT</i> and <i>GSK3B</i> genes.