Assessment of gene expression profiling and functional prioritization of nuclear envelope genes in Alzheimer's disease

AD affects millions of people each year. The pathology of this disease is not yet fully elucidated, making it difficult to develop effective therapeutic treatments and cures. Current literature suggests involvement of the NE in the molecular mechanism behind multiple neurodegenerative diseases. This study focused on unveiling transcriptomic changes of genes coding for NE-associated proteins in brains from patients with AD. A previously submitted dataset (GSE173955) containing RNA sequencing of hippocampal samples from AD (n = 10) and control (n = 8) patients was utilized for transcriptomic analysis. Functional enrichment analysis was performed using Reactome and DAVID functional annotation tools. Additionally, PPI analysis and gene prioritization were completed using the STRING database and Cytoscape. Gene expression analysis yielded 1,165 significantly upregulated genes and 1,299 significantly downregulated genes (adj. p < 0.05). Of these, 37 upregulated genes and 63 downregulated genes were shown to be associated with the NE. Reactome and DAVID analyses indicated that the most enriched functions were linked to NPC genes. Nup genes that were upregulated were NUP98, NUP160, and NUP188, and downregulated Nups were RAE1, and SEH1L. This study supports hypotheses, like the tau hypothesis, that disruption in nucleocytoplasmic transport plays an important role in AD.