Machine learning models identify ferroptosis-related genes as potential diagnostic biomarkers for Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a complex, and multifactorial neurodegenerative disease. Previous studies have revealed that oxidative stress, synaptic toxicity, autophagy, and neuroinflammation play crucial roles in the progress of AD, however, its pathogenesis is still unclear. Recent researches have indicated that ferroptosis, an iron-dependent programmed cell death, might be involved in the pathogenesis of AD. Therefore, we aim to screen correlative ferroptosis-related genes (FRGs) in the progress of AD to clarify insights into the diagnostic value. Interestingly, we identified eight FRGs were significantly differentially expressed in AD patients. 10,044 differentially expressed genes (DEGs) were finally identified by differential expression analysis. The following step was investigating the function of DEGs using gene set enrichment analysis (GSEA). Weight gene correlation analysis was performed to explore ten modules and 104 hub genes. Subsequently, based on machine learning algorithms, we constructed diagnostic classifiers to select characteristic genes. Through the multivariable logistic regression analysis, five features (RAF1, NFKBIA, MOV10L1, IQGAP1, FOXO1) were then validated, which composed a diagnostic model of AD. Thus, our findings not only developed genetic diagnostics strategy, but set a direction for further study of the disease pathogenesis and therapy targets.

STAT3-mediated ferroptosis is involved in α-synuclein pathology

“…To further investigate the molecular mechanisms between α-syn, STAT3 and ferroptosis, we used transcriptome sequencing of control and HMC3 cells exposed to α-syn oligomers. Gene set enrichment analysis (GSEA) is widely used to implement gene set enrichment testing, which is based on mainly enriched molecular signatures rather than differential gene expression 29,30 . GSEA showed a signi cant enrichment in the ferroptosis-related gene set.…”

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

“…Non-coding RNAs (ncRNAs) are involved in ferroptosis and AD progression, Tan et al (2023) identified 5 AD and ferroptosis-related hub genes, and constructed a novel ferroptosis-related signature models including mRNAs, miRNAs and lncRNAs. Deng et al (2022) screen correlative ferroptosis-related genes (FRGs) in the progress of AD by logistic regression.…”