Integrated Bioinformatics Analysis Identifies Pyroptosis-related Genes in Alzheimer’s Disease

Background: Recent studies have shown the association between Alzheimer’s disease (AD) and inflammation. Pyroptosis is an inflammatory type of programmed cell death, and it has been associated with AD. Herein, we aimed to explore the potential role of pyroptosis-related genes in AD, advancing the understanding of pyroptosis-related genes in AD pathogenesis. Methods: : Based on the gene expression profile in GSE5281, we screened for differentially expressed genes (DEGs), performed a weighted gene correlation analysis (WGCNA), and identified the most AD-related module. After intersecting the hub genes in this module with 52 pyroptosis-related genes, we obtained the key genes to construct a least absolute shrinkage and selection operator (LASSO) model for AD. We also constructed a CASP6-focused interaction network including several hub genes. The LASSO model and expression of CASP6 were evaluated in GSE122063 and GSE132903. Results: : Through WGCNA, four functional modules were identified, of which the brown module is most significantly related to AD (correlation coefficient=0.93, P=4e-13). CASP6 is aberrantly highly expressed in AD and closely connected with hub genes in the brown module. Seven genes (CASP6, BAK1, CASP5, CHMP4B, CHMP4C, IRF2, PLCG1) were identified as key genes, and the LASSO model based on key genes can predict AD with medium-to-high accuracy in train, test and validation set (AUC=0.898, 0.811, 0.857, respectively). Conclusions: : Highly expressed CASP6 interact with other pyroptosis-related genes in AD, shedding light on the potential role of pyroptosis in AD pathogenesis.