Work

Identification of m5C-associated gene signatures in Alzheimer's disease and their relationship with immune infiltration

Year: 2026

Type: article

Abstract: Background Alzheimer's disease (AD) is a diverse and advancing neurodegenerative disorder that represents the prevalent type of cognitive decline. The objective of this research is to explore the possible impacts of genes related to 5-Methylcytosine (m5C) in Alzheimer's disease (AD). Methods By combining data from two Gene Expression Omnibus (GEO) datasets (GSE132903, GSE118553), the genes that were differentially expressed and associated with AD were extracted. Subsequently, m5C-related genes with differential expression (m5CRDEGs) were detected and their potential biological functions were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Association analysis and receiver operating characteristic curves (ROC) were used to analyze the m5CRDEGs.The expression and diagnostic efficiency of m5CRDEGs were validated in two external datasets (GSE33000, GSE122063). Moreover, the STRING database was utilized to construct a network of protein-protein interactions (PPIs), and Cytoscape was employed to visualize the hub genes. In the end, we analyzed the CIBERSORT algorithm to estimate the proportions of immune cell subsets. Results We identified five m5CRDEGs (ZBTB4, MBD4, ZBTB33, NEIL1, TDG) that were closely related to apoptosis, autophagy, circadian rhythm, acid metabolism, and p38MAPK pathway. The ROC curves demonstrated that ZBTB4 could function as a predictive hub gene for AD. In addition, our subsequent analysis of the miRNA/TF-mRNA networks showed that gene MBD4 had the most interaction with other m5CRDEGs based on five algorithms. Moreover, there was a significant association between hub gene expression and the abundance of CD8 + T cells and monocytes in our research. Conclusion New signatures from m5CRDEGs could potentially be used as biomarkers for AD, revealing a connection to the immune microenvironment that sheds light on the molecular mechanisms of AD and could support future research and treatment advancements.

Source: IBRO Neuroscience Reports

DOI: 10.1016/j.ibneur.2026.10.008

Authors: Pan Ai, Xuyang Wang, Hui Shi, Anshi Wu, Jing Wang

Institutions: Capital Medical University, Beijing Chao-Yang Hospital, Capital Medical University

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,400