Lipidomic reveals potential mediators of associations between lead exposure and Alzheimer's disease.

IF 2.7 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2025-10-16 DOI:10.1080/15376516.2025.2576266

Hong-Mei Gan, Cui-Ju Liu, Rong-Juan Jiang, Zhi-Yong Zhang, Bo Qian

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引用次数: 0

Abstract

Previous studies have identified associations between lead (Pb) exposure and the incidence of Alzheimer's disease (AD), yet the underlying mechanisms are still missing. This investigation verified the association between Pb exposure burden and AD risk in a small case-control study. Using a nontargeted quantification lipidomic assay, the role of 3034 lipid metabolites in the associations between Pb exposure and AD risk was also explored. The results showed that serum Pb levels in AD patients were significantly higher than in control individuals. Meanwhile, serum Pb levels were positively associated with an increased risk of AD (OR = 1.10, 95% CI = 1.04-1.15). Lipidomic assay identified that four lipid metabolites, including phosphatidylcholine (PC) (33:2e), diacylglycerol (DG) (19:1e), sphingomyelins (SM) (d38:4), and phosphoserine (PS) (39:1), were significantly altered in the serum of AD patients. Among them, PC(33:2e) and SM(d38:4) were positively correlated with serum Pb levels. Moreover, PC(33:2e) and SM(d38:4) demonstrated mediation contributions of 60.49% and 20.38%, respectively, in the association between Pb exposure and AD incidence. Network toxicology suggests that Pb exposure may affect lipid metabolic processes in AD by modulating the activation of the MAPK, PI3K-Akt, AMPK, mTOR, and autophagy pathways. Our findings reveal novel insights into AD pathogenesis, suggesting that lipid metabolites may play a mediating role in the association between Pb exposure burden and AD risk.

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脂质组学揭示了铅暴露与阿尔茨海默病之间的潜在关联介质。

先前的研究已经确定了铅（Pb）暴露与阿尔茨海默病（AD）发病率之间的关联，但其潜在机制仍然缺失。这项调查在一项小型病例对照研究中证实了铅暴露负担与AD风险之间的关联。通过非靶向定量脂质组学分析，研究人员还探讨了3034种脂质代谢物在铅暴露与AD风险之间的作用。结果表明，AD患者血清铅水平明显高于对照组。同时，血清铅水平与AD风险增加呈正相关（OR = 1.10, 95% CI = 1.04-1.15）。脂质组学分析发现，AD患者血清中的4种脂质代谢物，包括磷脂酰胆碱（PC）（33:2e）、二酰基甘油（DG）（19:1e）、鞘磷脂（SM）（d38:4）和磷酸丝氨酸（PS）（39:1）显著改变。其中，PC（33:2 2）和SM（38:4）与血清铅水平呈正相关。此外，PC（33:2e）和SM（38:4）在铅暴露与AD发病率之间的中介作用分别为60.49%和20.38%。网络毒理学表明，铅暴露可能通过调节MAPK、PI3K-Akt、AMPK、mTOR和自噬途径的激活来影响AD的脂质代谢过程。我们的研究结果揭示了阿尔茨海默病发病机制的新见解，表明脂质代谢物可能在铅暴露负担与阿尔茨海默病风险之间的关联中发挥中介作用。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.