Six mitophagy-related hub genes as peripheral blood biomarkers of Alzheimer’s disease and their immune cell infiltration correlation

Abstract

BackgroundAlzheimer’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.MethodUtilizing 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).ResultsOur 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.ConclusionOur 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.

A review and analysis of key biomarkers in Alzheimer’s disease

“… Zhang et al (2023a) used PPI network, random forest, and two machine learning algorithms to obtain hub mitochondrial-related differentially expressed genes (MitoDEGs) closely related to AD. Zhao et al (2023) identified six mitophagy-related hub genes (MRHGs) that be used as valuable diagnostic biomarkers for AD.…”

“…Sirkis et al (2023) explores the association of early-onset Alzheimer's disease (EOAD) with specific peripheral immune signatures, and single-cell RNA sequencing identified significant expansion of a CD4 T cell termed interferon (IFN) signalingassociated gene (ISAG) hi T cells. Lin et al (2023) has explored the association between high-fat diet and AD and T2D. Analysis of singlecell RNA-seq (scRNA-seq) data indicated C4b is astrocyte-specific.…”

Bioinformatic identification and experiment validation reveal 6 hub genes, promising diagnostic and therapeutic targets for Alzheimer’s disease

“…Microarray analysis and gene sequencing have been widely applied to explore the potential biomarkers or therapeutic targets of AD. After using 3 microarray datasets to screen mitogen-related hub genes in peripheral blood mononuclear cells of AD patients, 53 differentially expressed genes (DEGs) of AD are identified, which may serve as possible biomarkers for the diagnosis of AD [ 11 ]. LncRNA RP11-59 J16.2 may be a molecular target for AD, according to microarray analysis of blood from AD patients and healthy controls to determine LncRNA and mRNA expression profiles [ 12 ].…”