Identifying microglia-derived NFKBIA as a potential contributor to the pathogenesis of Alzheimer's disease and age-related macular degeneration.

Abstract

BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) place considerable health burden on affected individuals and significant economic burden on society.ObjectiveThis study aims to explore the shared cellular and molecular mechanisms underlying the pathogenesis of AD and AMD.MethodsThe investigation in this study is conducted via single-cell and bulk tissue transcriptomic analysis. Transcriptomic datasets of AD and AMD were obtained from the GEO database. The shared differentially expressed genes (DEGs) in control and AD- and AMD-affected samples were identified. Functional enrichment analysis for DEGs was subsequently performed. Then, the protein-protein interaction (PPI) network of these DEGs was established via the STRING database and hub genes of this network were identified by Cytoscape software. Single-cell transcriptomic analysis was performed using Seurat R package to explore their expression in different cell types.ResultsDifferential analysis identified 127 shared DEGs of the two diseases, including 71 upregulated and 56 downregulated genes. Upregulated DEGs were enriched in inflammation, gliogenesis, cell apoptosis, and response to bacterial and viral infection and downregulated DEGs were enriched in mitochondrial function and energy production. PPI network and Cytoscape determined 10 hub genes, of which the NFKBIA gene was associated with the severity of both AD and AMD. Moreover, single-cell transcriptomic analysis showed that NFKBIA was highly expressed in microglia from disease-affected tissues.ConclusionsThe findings indicated that microglia with high NFKBIA expression were important contributors to the progression of both AD and AMD. Microglia-derived NFKBIA might serve as a potential therapeutic target for AD and AMD.