Investigating the relationship between DPYSL4 and FOLR3 genes expression with late-onset Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a disorder related to the heterogeneous degeneration of the brain, the prevalence of which is increasing worldwide. So far, many studies have been conducted on the regulation of the expression of functional genes involved in crucial pathways and mechanisms, and they indicate that a small change can eventually cause the central nervous system (CNS) to undergo pathogenic changes. Signaling pathways of semaphorins are among the pathways that play an important role in the formation of neuronal synapses and the structuring of axons in neurons in the hippocampus. On the other hand, the direct relationship of semaphorin3a with the formation of neurofibrillary tangles (NFT) and tau protein hyperphosphorylation has been identified. The regulation of homocysteine levels and the pathways leading to it are among the pathways influencing AD pathogenesis. The potential gene DPYSL4 is involved in the signaling pathway of semaphorins and the FOLR3 gene is involved in the regulation of homocysteine levels, which can be suitable candidates for studying AD. In this research, we tried to investigate DPYSL4 and FOLR3 genes in AD in peripheral blood related to the possible mechanism of AD pathogenesis. Methods: Mechanisms and pathways involved in the pathogenesis of AD were identified and studied using a literature review. In the meantime, more attention was paid to pathways that have been newly introduced and fewer studies have been done on them. The semaphorin-plexin signaling pathway in neuronal formation and structuring is one of the potential pathways that have been studied less in AD. DPYSL4 gene was considered one of the identified genes involved in this pathway to study its expression levels. On the other hand, although the regulation of homocysteine levels is more known, the regulation of its levels using folate receptors has also recently been proposed. The FOLR3 gene is one of the genes involved in the regulation of homocysteine levels, which was considered in this study by examining the expression levels. The results of the expression of the desired genes will be measured together, and expression correlation plots were demonstrated in the blood of patients compared to the healthy controls. The quantitative polymerase chain reaction technique was also used to investigate the expression of these regulatory factors in the peripheral blood of 50 AD patients and 50 controls. Results: by examining the expression levels of DPYSL4 and FOLR3 genes in the peripheral blood of people with AD compared to healthy controls, it was concluded that the expression levels of these two genes do not show significant changes in the blood. It is interesting to note that these two genes were significantly correlated in terms of expression, and the expression levels of the DPYSL4 gene were also correlated with the age of the patients.