Abstract
BACKGROUND: Alzheimer's disease (AD), a neurodegenerative disorder with progressive symptoms, seriously endangers human health worldwide. AD diagnosis and treatment are challenging, but molecular biomarkers show diagnostic potential. This study aimed to investigate AD biomarkers in the peripheral blood. METHOD: Utilizing three microarray datasets, we systematically analyzed the differences in expression and predictive value of mitophagy-related hub genes (MRHGs) in the peripheral blood mononuclear cells of patients with AD to identify potential diagnostic biomarkers. Subsequently, a protein-protein interaction network was constructed to identify hub genes, and functional enrichment analyses were performed. Using consistent clustering analysis, AD subtypes with significant differences were determined. Finally, infiltration patterns of immune cells in AD subtypes and the relationship between MRHGs and immune cells were investigated by two algorithms, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). RESULTS: Our study identified 53 AD- and mitophagy-related differentially expressed genes and six MRHGs, which may be potential biomarkers for diagnosing AD. Functional analysis revealed that six MRHGs significantly affected biologically relevant functions and signaling pathways such as IL-4 Signaling Pathway, RUNX3 Regulates Notch Signaling Pathway, IL-1 and Megakaryocytes in Obesity Pathway, and Overview of Leukocyteintrinsic Hippo Pathway. Furthermore, CIBERSORT and ssGSEA algorithms were used for all AD samples to analyze the abundance of infiltrating immune cells in the two disease subtypes. The results showed that these subtypes were significantly related to immune cell types such as activated mast cells, regulatory T cells, M0 macrophages, and neutrophils. Moreover, specific MRHGs were significantly correlated with immune cell levels. CONCLUSION: Our findings suggest that MRHGs may contribute to the development and prognosis of AD. The six identified MRHGs could be used as valuable diagnostic biomarkers for further research on AD. This study may provide new promising diagnostic and therapeutic targets in the peripheral blood of patients with AD.