Genetic markers associated with ferroptosis in Alzheimer's disease.

Abstract

Ferroptosis is implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and vascular dementia, implying that it may have a regulatory effect on the progression of these diseases. However, the specific role of ferroptosis-related genes (FRGs) in Alzheimer's disease (AD) is not yet fully understood. The aim of the study was to detect ferroptosis related genes with regulatory functions in the disease and explore potential mechanisms in AD. Hub FRGs were obtained through multiple algorithms based on the GSE5281 dataset. The screening process was implemented by R packages including limma, WGCNA, glm and SVM-RFE. Gene Ontology classification and pathway enrichment analysis were performed based on FRGs. Biological processes involved with hub FRGs were investigated through GSVA and GSEA methods. Immune infiltration analysis was performed by the R package CIBERSORT. Receiver operating characteristic curve (ROC) was utilized to validate the accuracy of hub FRGs. The CeRNA network attempted to find non-coding RNA transcripts which may play a role in disease progression. DDIT4, MUC1, KLHL24, CD44, and RB1 were identified as hub FRGs. As later revealed by enrichment analysis, the hub FRGs had important effects on AD through involvement in diverse AD pathogenesis-related pathways such as autophagy and glutathione metabolism. The immune microenvironment in AD shows increased numbers of resting NK cells, macrophages, and mast cells, with decreased levels of CD8 T cells when compared to healthy samples. Regulatory T cells were positively correlated with MUC1, KLHL24, and DDIT4 expression, while RB1 showed negative correlations with eosinophils and CD8 T cells, suggesting potential roles in modulating the immune environment in AD. Our research has identified five hub FRGs in AD. We concluded that ferroptosis may be involved in the disease.