Bioinformatic Analysis and Experimental Validation of Ubiquitin-Proteasomal System-Related Hub Genes as Novel Biomarkers for Alzheimer's Disease

作者：Yuting Zhang, Jie Wu, Guoxing You, Wenjie Guo, Yupeng Wang, Zhiyong Yu, Yan Geng, Qinghua Zhong, Jie Zan, Linbo Zheng · 发表于：Journal of Integrative Neuroscience · 年份：2023 · DOI：10.31083/j.jin2206138 · 被引用次数：3 · 研究领域：Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms、Ferroptosis and cancer prognosis

BACKGROUND: Alzheimer's disease (AD) is a common progressive neurodegenerative disease. The Ubiquitin-Protease system (UPS), which plays important roles in maintaining protein homeostasis in eukaryotic cells, is involved in the development of AD. This study sought to identify differential UPS-related genes (UPGs) in AD patients by using bioinformatic methods, reveal potential biomarkers for early detection of AD, and investigate the association between the identified biomarkers and immune cell infiltration in AD. METHODS: The differentially expressed UPGs were screened with bioinformatics analyses using the Gene Expression Omnibus (GEO) database. A weighted gene co-expression network analysis (WGCNA) analysis was performed to explore the key gene modules associated with AD. A Single-sample Gene Set Enrichment Analysis (ssGSEA) analysis was peformed to explore the patterns of immune cells in the brain tissue of AD patients. Real-time quantitative PCR (RT-qPCR) was performed to examine the expression of hub genes in blood samples from healthy controls and AD patients. RESULTS: ) that are strongly correlated with the clinical features of AD were used to construct risk score prediction markers to diagnose and predict the severity of AD. Subsequently, we analyzed the patterns of immune cells in the brain tissue of AD patients and the associations between immune cells and the three key UPGs. Finally, the risk score model was verified in several datasets of AD and showed good accura...