Identification and validation of aryl hydrocarbon receptor-related key genes in Alzheimer's disease: an integrated analysis of bulk RNA sequencing and single-cell RNA sequencing

Background Alzheimer's disease (AD) is an irreversible and continuously progressive neurodegenerative disorder. The aryl hydrocarbon receptor (AhR) has been shown to be associated with this disease, but the specific molecular mechanism has not yet been fully elucidated. Methods This study identified key genes through differential expression analysis combined with machine learning and gene expression profiling. Subsequent analyses included functional annotation and immune infiltration feature analysis. Subsequently, single-cell RNA sequencing (scRNA-seq) was used to determine the specific cell types where these genes were differentially expressed, and the intercellular communication was further investigated. The expression levels were verified through reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results This study identified 5 key genes ( ADRB3 , ADCY2 , FGF6 , PRKACB and SOS1 ). Gene set enrichment analysis (GSEA) revealed that pathways such as epithelial-mesenchymal transition and TGF-β signaling were associated with specific key genes; immune infiltration analysis determined that regulatory T cells (Tregs) were the most widely associated immune cell type with the key genes. In AD, the interaction between the two key cell types (CD4 T cells and NKT cells) increased. RT-qPCR confirmed the downregulation of ADCY2 and FGF6 and the upregulation of SOS1 in AD. Conclusion The identification of these key genes has provided new insights into their potential pathophysiological mechanisms and offered valuable reference data for the identification of potential therapeutic targets.