Transcriptional signature genes associated with synapse, mitochondria, and cytoskeleton of hippocampal and entorhinal cortex neurons in Alzheimer’s brain

Alzheimer’s disease (AD) is one of the major causes of dementia in the elderly worldwide. However, the causes of the disease are not fully understood. The pathological hallmarks of AD are microtubule destabilization, synaptic degeneration, and mitochondrial dysfunction. The neurons especially in the hippocampus (HP) and entorhinal cortex (EC) are those selectively vulnerable cells and thus affect the learning and memory of patients. Several previous studies had attempted to understand the disease by studying gene expression profiles. In this study, we performed a transcriptional analysis of five datasets from HP tissue (GSE1297, GSE28146, GSE36980, GSE48350, and GSE5281) and two datasets from EC tissues (GSE48350 and GSE5281). We focused on the differential gene expression (DGE) in the structure of synapse, mitochondria, and cytoskeleton. We identified 56 common genes in HP and 83 common genes in EC. Of which, 58 common genes were identified in the synapse, mitochondria, and cytoskeleton cellular compartments. These gene-encoding proteins were mapped to the protein-protein interaction network and identified hub genes using Cytoscape. We identified a subnetwork of 129 nodes and 122 edges, of which 10 genes have been reported to be associated with AD. The largest hub of the protein-protein interaction network was ATP5B followed by UQCRQ. Our study demonstrated the common DEGs in three cellular compartments including synapse, mitochondria and cytoskeleton, and identified the genes which may be important in AD progression.