INTRODUCTIONStudies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear.METHODSWe exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population‐based Rotterdam Study.RESULTSDE exposure resulted in an almost four‐fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2–related factor 2 signaling in responses to air pollutants.DISCUSSIONThis study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses.Highlights Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE‐exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population‐based study.

中文翻译：

---

转录组学和表观基因组分析揭示了阿尔茨海默病在体外和基于人群的数据中对柴油排放的反应发生了变化


引言学生将居住在主要道路附近与阿尔茨海默病 （AD） 风险相关联。然而，造成这种联系的机制仍不清楚。方法将健康个体和 AD 患者的嗅粘膜 （OM） 细胞暴露于柴油排放物 （DE）。评估暴露的细胞毒性，进行 mRNA 、 miRNA 表达和 DNA 甲基化分析。使用基于人类群体的鹿特丹研究的数据验证了发现的改变途径.RESULTSDE 暴露导致 AD OM 细胞的反应高出近四倍，表明对 DE 效应的敏感性增加。甲基化分析检测到不同的 DNA 甲基化模式，揭示了新的暴露靶标。通过分析来自鹿特丹研究队列的数据验证了研究结果，并证明了核因子红细胞 2 相关因子 2 信号在响应空气污染物中的关键作用。讨论这项研究确定了空气污染暴露生物标志物，并确定了暴露激活的关键途径。数据表明，由于细胞防御受损，AD 个体可能面临更高的风险。亮点 健康细胞和 AD 嗅觉细胞对 DE 暴露的反应不同。AD 细胞对 DE 暴露高度敏感。NRF2 氧化应激反应在空气污染暴露时高度激活。DE 暴露的 AD 细胞激活未折叠的蛋白质反应通路。一项基于人群的研究也证实了主要发现。