Developing diagnostic biomarkers for Alzheimer's disease based on histone lactylation-related gene
Shaobo Guo,
Wenhui Zhu,
Yuting Bian,
Zhikai Li,
Heng Zheng,
Wenlong Li,
Yi Yang,
Xuzheng Ji,
Biao Zhang
Affiliations
Shaobo Guo
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
Wenhui Zhu
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
Yuting Bian
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
Zhikai Li
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
Heng Zheng
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China; Zhenjiang Hospital of Chinese Traditional And Western Medicine, Zhenjiang, China
Wenlong Li
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China; Liyang Hospital of Chinese Medicine, Liyang, China
Yi Yang
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
Xuzheng Ji
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China
Biao Zhang
The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China; Corresponding author. The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Geriatric, Nanjing, China.
Background: Research underscores the significant influence of histone lactylation pathways in the progression of Alzheimer's disease (AD), though the molecular mechanisms associated with histone lactylation-related genes (HLRGs) in AD are still insufficiently investigated. Methods: This study employed datasets GSE85426 and GSE97760 to identify candidate genes by intersecting weighted gene co-expression network analysis (WGCNA) module genes with AD-control differentially expressed genes (DEGs). Subsequently, machine learning refined key genes, validated by receiver operating characteristic (ROC) curve performance. Gene-set enrichment analysis (GSEA) explored the molecular mechanisms of these diagnostic markers. Concurrently, the association between the diagnostic genes and both differential immune cells and immune responses was examined. Furthermore, a ceRNA and gene-drug network was developed. Finally, the expression of the selected genes was validated using brain tissues from AD model mice. Results: This study identified five genes (ARID5B, NSMCE4A, SESN1, THADA, and XPA) with significant diagnostic utility, primarily enriched in olfactory transduction and N-glycan biosynthesis pathways. Correlation analysis demonstrated a strong positive association between all diagnostic genes and naive B cells. The ceRNA regulatory network comprised 7 miRNAs, 2 mRNAs, and 25 lncRNAs. Additionally, 33 drugs targeting the diagnostic genes were predicted. Following expression validation through training and validation sets, three genes (ARID5B, SESN1, XPA) were ultimately confirmed as biomarkers for this study. RT-qPCR and Western blot analyses revealed upregulated expression of ARID5B, SESN1, and XPA in the cerebral tissue of AD model mice. Conclusion: Three histone lactylation-linked genes (ARID5B, SESN1, XPA) were identified as potential AD biomarkers, indicating a strong association with disease progression.
