Mutational Screening in Exon 6 of the PSEN2 Gene in Iranian Patients with Late-Onset Alzheimer\'s Disease

Background and Aims: One of the most important genes involved in Alzheimer's disease (AD) is the presenilin2 (PSEN2) gene, which is one of the main constituents of the gamma-secretase complex. Mutations in this gene promote the formation of amyloid plaques resulting in AD. The study aimed to evaluate the mutation variant in exon 6 of the PSEN2 gene in patients with Late-Onset AD (LOAD). Due to the important role of the PSEN2 gene in the formation of beta-amyloid aggregates and the investigation involves an association between PSEN2 mutations and their pathogenicity in LOAD progression, we presented this exon as a more efficient alternative. Materials and Methods: The thirty patients with LOAD and 16 healthy subjects as a control group were involved in this experimental study. DNA was extracted from blood samples and purified. The desired gene fragment was propagated using polymerase chain reaction and the products were electrophoresed and the results were analyzed. Result: A novel mutation was found in PSEN2 IVS6 + 30 G → C at the intron region of exon 6 in 20 cases of patients suffering from LOAD and 12 subjects in control cohort. In this mutation a guanine base was substituted by cytosine base which this position was 30 nucleotides separated from coding region. Conclusions: The novel mutation was identified in both studied groups. These findings reveal no relationship between PSEN2 mutation and pathogenicity of LOAD disease. However, further studies are required to find the role of PSEN2 mutation in LOAD progression.