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

• Published in: International journal of molecular sciences 2024-09, Vol.25 (18), p.10228
• Main Authors: Toral-Rios, Danira, Pichardo-Rojas, Pavel, Ruiz-Sánchez, Elizabeth, Rosas-Carrasco, Óscar, Carvajal-García, Rosa, Gálvez-Coutiño, Dey Carol, Martínez-Rodríguez, Nancy Lucero, Rubio-Chávez, Ana Daniela, Alcántara-Flores, Myr, López-Ramírez, Arely, Martínez-Rosas, Alma Rosa, Ruiz-Chow, Ángel Alberto, Alonso-Vanegas, Mario, Campos-Peña, Victoria
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Alleles; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoprotein E4 - genetics; Apolipoproteins; Convulsions & seizures; Cyclin-dependent kinases; Development and progression; Disease; Drug Resistant Epilepsy - drug therapy; Drug Resistant Epilepsy - genetics; Epilepsy; Epilepsy, Temporal Lobe - drug therapy; Epilepsy, Temporal Lobe - genetics; Female; Genes; Genetic aspects; Genetic Predisposition to Disease; Genotype & phenotype; Glycogen Synthase Kinase 3 beta - genetics; Glycogen Synthase Kinase 3 beta - metabolism; Haplotypes; Health aspects; Health risk assessment; Humans; Kinases; Male; Middle Aged; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Tau proteins; tau Proteins - genetics; tau Proteins - metabolism; Temporal lobe epilepsy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.