Benzo[a]pyrene (BaP), a common environmental neurotoxicant, has been linked to neurodegenerative diseases, yet its role in Alzheimer's disease (AD) remains unclear.
Objective
This study integrated network toxicology, machine learning, single-cell transcriptomics, and bibliometric analysis to explore BaP's mechanistic role in AD.
Methods
A 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.
Results
Targets 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.
Conclusions
BaP 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 environmental toxicants to AD pathogenesis.
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