Uncovering the toxicological impact of benzo[a]pyrene on Alzheimer's disease via network toxicology, machine learning, and single-cell transcriptomics

作者：Wencai Wang, XinYi Wei, Zhonghua Sun, Xuemei Zhang, Di Pan, Xiangxiang Hong, Xianfeng Li, Dan Yang · 发表于：Journal of Alzheimer s Disease · 年份：2025 · DOI：10.1177/13872877251405468 · 被引用次数：6 · 研究领域：Alzheimer's disease research and treatments、Single-cell and spatial transcriptomics、Neuroinflammation and Neurodegeneration Mechanisms

BackgroundBenzo[a]pyrene (BaP), a common environmental neurotoxicant, has been linked to neurodegenerative diseases, yet its role in Alzheimer's disease (AD) remains unclear.ObjectiveThis study integrated network toxicology, machine learning, single-cell transcriptomics, and bibliometric analysis to explore BaP's mechanistic role in AD.MethodsA total of 253 BaP-AD common targets were identified and analyzed via GO/KEGG enrichment and PPI network construction. Key genes were screened using GEO-based AD differential expression data and machine learning (LASSO and SVM). Molecular docking assessed BaP-target interactions. Cell-type-specific expression was analyzed using single-cell RNA-seq (GSE157827). ROC curves evaluated diagnostic value, and bibliometrics explored research trends.ResultsTargets were enriched in oxidative stress and MAPK/PI3K-Akt pathways. EGFR and HSP90AB1 were identified as core targets, with strong BaP binding affinities (-8.4 and -11.7 kcal/mol, respectively). EGFR was highly expressed in astrocytes and OPCs; HSP90AB1 in astrocytes and neurons. EGFR had better diagnostic performance (AUC = 0.781). Bibliometric analysis showed increasing attention on EGFR's role in AD.ConclusionsBaP may promote AD by targeting EGFR and HSP90AB1, affecting inflammation, proteostasis, and survival pathways. Notably, EGFR may serve emerge a promising biomarker for early diagnosis and therapeutic intervention in AD. This study revealed the underlying molecular mechanisms linking...