Identification of key genes and pathways involved in Alzheimer’s disease through bioinformatic analysis

AbstractBackgroundAlthough there has been an intensive research on the molecular mechanisms of AD, there’re still unexplored pathways due to the heterogeneity of the disease mechanisms and variations in experimental approaches. Therefore, bioinformatics to would be helpful in deciphering the key gene expression patterns in existing datasets, which will eventually serve as biomarkers for AD.MethodIn this study, we aimed to identify the key genes and miRNAs involved in AD via bioinformatic analyses. We selected the GEO dataset GSE48350, which contains the microarray data collected from entorhinal cortex (EC), hippocampus (H), postcentral gyrus (PCG) and superior frontal gyrus (SFG) of the 80 AD and 173 healthy brains. We first identified the differentially expressed genes (DEGs) using the GEO2R web tool. Then, functional enrichment analysis (FEA) was performed by using DAVID. Protein‐protein interaction (PPI) networks were drawn by using STRINGdb and the hub proteins were detected by using the Cytohubba module in the Cytoscape program. miRNA detection was performed by using the miRDB web tool.ResultWe identified 12, 49, 69, 7, and 26 downregulated and 16, 51, 245, 10, and 44 upregulated genes as in all parts of the brain, EC, H, PCG and SFG regions, respectively. PPI analysis revealed the top three hub proteins as: GFAP, CXCR4, FOS in the EC; SNAP25, GRIN1, SLC32A1 in H; GFAP, SST, CXCR4 in FG regions and GFAP, SLC32A1, SST in the whole brain. According to FEA, the identified genes are involved in chemical synaptic transmission, neurotransmitter release, extracellular matrix organization, and inflammatory response. Upon analysis of the miRNA target database, we identified seven miRNAs targeting these genes. The most exciting miRNA turns out to be hsa‐miR548 family, since it targets CXCR4, FOS and GFAP.ConclusionThe identified DEGs may serve as biomarkers and drug targets for AD. Therefore, additional experiments on expressions of these genes in the plasma or cerebrospinal fluid samples of the patients should be performed. Also, miR‐548 family should be explored as a candidate drug target.