Analysis of relationship between miR-361, ATAD1 and HOMER1expression with late-onset Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. So far, many studies have been done on regulation of the inflammatory functional genes and growth factors expression and indicate that a small change can eventually cause pathogenic changes in the central nervous system (CNS). Emerging evidence points to the possibility that the Glutamatergic signaling pathway undergoes pathological alterations and contributes to pathological hallmarks of AD. ATAD1 and HOMER1 genes are controls the internalization of excitatory, glutamatergic AMPA receptors by disassembling complex between the AMPA receptor-binding protein, GRIP1, and the AMPA receptor. We used bioinformatics and experimental methods in this research to explore ATAD1/HOMER1 can capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. Methods: Through the miRTarBase and miRWalk databases, which provide valid miRNAs, miR-361 was selected as a miRNA that targets the ATAD1 and HOMER1 target gene. The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD, and corresponding controls were downloaded. R software was used to identify mRNAs and miRNAs with different expressions. Among the results, the expression of the desired genes was measured together, and diagrams of expression correlation were drawn in the brain tissue of patients compared to the brain tissue of healthy controls. Real-time PCR was also used to evaluate the expression of the ATAD1, HOMER1 and miR-361 in the peripheral blood (PB) of 50 AD patients and 50 control subjects. Results: Bioinformatics assessment showed that ATAD1 and HOMER1 act as regulatory of synaptic plasticity by control Glutamatergic receptors expression in temporal cortex (TC) tissue sample by decreasing expression. Furthermore, in peripheral blood (PB) specimens from individuals suffering from AD and normal controls, we found no substantial differences in ATAD1 and HOMER1 expression patterns. Furthermore, we discovered reduced amounts of hsa-miR-361-5p in AD patients’ PB samples compared to control subjects, as was the case in TC tissue. Finally, it was shown that has-miR-361-5p to be effective in identifying AD patients from healthy controls, based on the assessment of the receiver operating characteristic (ROC).