Machine learning identification and immune infiltration of disulfidptosis‐related Alzheimer's disease molecular subtypes

BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder. Disulfidptosis is a newly discovered form of programmed cell death that holds promise as a therapeutic strategy for various disorders. However, the functional roles of disulfidptosis‐related genes (DRGs) in AD remain unknown. METHODS: Microarray data and clinical information from patients with AD and healthy controls were downloaded from the Gene Expression Omnibus database. A thorough examination of DRG expression and immune characteristics in both groups was performed. Based on the identified DRGs, we performed an unsupervised clustering analysis to categorize the AD samples into various disulfidptosis‐related molecular clusters. Weighted gene co‐expression network analysis was performed to select hub genes specific to disulfidptosis‐related AD clusters. The performances of various machine learning models were compared to determine the optimal predictive model. The predictive ability of the optimal model was assessed using nomogram analysis and five external datasets. RESULTS: Eight DRGs showed differential expression between the AD and control samples. Two different molecular clusters were identified. The immune cell infiltration analysis revealed distinct differences in the immune microenvironment of the two clusters. The support vector machine model showed the highest performance, and a panel of five signature genes was identified, which showed excellent performance on the external validation datasets. The nomogram analysis also showed high accuracy in predicting AD. CONCLUSION: We identified disulfidptosis‐related molecular clusters in AD and established a novel risk model to assess the likelihood of developing AD. These findings revealed a complex association between disulfidptosis and AD, which may aid in identifying potential therapeutic targets for this debilitating disorder.