In this study, we first conducted transcriptome sequencing analysis of SH-SY5Y cells after PS2 gene knockdown and then performed Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and Disease Ontology (DO) enrichment analyses to screen the differentially expressed genes (DEGs) possibly involved in the regulation of mitochondrial dynamics and the pathogenesis of AD. Here, PSEN2 is linked to Alzheimer disease.