Genes related to neurotransmitter receptors as potential biomarkers for Alzheimer's disease

Introduction: Alzheimer's disease (AD) is a leading cause of dementia and is rapidly emerging as one of the costliest and most burdensome diseases. Neurotransmitter receptors play a vital role in many neuronal processes, primarily regulating signal inhibition within the brain to facilitate cell communication. Objectives: Our research aims to identify potential biomarkers associated with AD and how these biomarkers impact immune infiltration. Methods: We extracted mRNA expression data from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were employed to identify hub genes as biomarkers in AD. The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Variation Analysis (GSVA) were used for functional enrichment. Furthermore, we examined 22 immune cell types infiltration using "CIBERSORT". Results: In this study, we identified 70 neurotransmitter receptor genes showing differential expression in AD: 22 were up-regulated, and 48 were down-regulated. Functional analyses indicated these genes were involved in essential biochemical pathways, including G protein-coupled receptors, neurotransmitter receptor activity, and ion channel interactions. WGCNA generated three co-expression modules, with one demonstrating the strongest association with AD. Five key NRGs (HTR3C, HTR3E, ADRA2A, HTR3A, and ADRA1D) were identified using a combination of differential genes. These genes have better diagnostic value by ROC analysis. Immune infiltration analysis showed that these genes were closely associated with the levels of resting mast cells, activated natural killer (NK) cells, and plasma cells in AD compared to controls. Conclusion: Our study identified five NRGs (ADRA1D, ADRA2A, HTR3A, HTR3C, and HTR3E) with significant associations with AD. These findings may offer promising sights for further studies.