Genetic Characterization of MAPT Exon 6 Variants in Indonesian Patients with Vascular Dementia: A Cross-Sectional Sequencing Study

Abstract

Background The microtubule-associated protein tau (MAPT) gene plays a critical role in neuronal microtubule stabilization and has been widely implicated in neurodegenerative disorders, including vascular dementia. However, the molecular characterization of MAPT gene variants in patients with vascular dementia remains limited, particularly in Southeast Asian populations. This study aims to characterize MAPT gene variants in Indonesian patients with vascular dementia by screening selected coding exons using direct Sanger sequencing. Methods This cross-sectional sequencing study included 17 patients with clinically diagnosed vascular dementia. Genomic DNA extracted from peripheral blood was used to screen selected coding exons of the MAPT gene by direct Sanger sequencing. The identified variants were characterized by their genotype and allele frequencies, and individual clinical characteristics were descriptively presented according to genotype. Results Three sequence variants were identified by screening selected coding exons of the MAPT gene, including rs63750222 (exon 4A), rs2258689 (exon 6), and c.1617G > A (exon 9). Among these, rs2258689 was the only variant that exhibited polymorphism within the study population. The C/C genotype was the most frequent (58.8%), followed by T/C (29.4%) and T/T (11.8%), while the C allele predominated (73.5%) over the T allele (26.5%). Individual distributions of age, MoCA-Ina, and CDR-SB scores demonstrated substantial variability across genotype groups. Conclusion This study provides the first molecular characterization of MAPT gene variants in Indonesian patients with vascular dementia. The identification of rs2258689 as the only polymorphic variant establishes baseline molecular data for future genetic and functional studies.