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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD.
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Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD.

机译：婴儿暴露于环境金属铅（Pb）后，老年猴的阿尔茨海默氏病（AD）样病理：AD的发育起源和环境联系的证据。

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摘要

The sporadic nature of Alzheimer's disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic beta-amyloid (Abeta) product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 (beta-site APP cleaving enzyme 1)] as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD.
机译：阿尔茨海默氏病（AD）的零星性质要求建立可能导致AD发病机制的环境联系。但是，触发因素及其作用的时间未知。啮齿类动物的最新研究表明，在大脑发育过程中接触铅（Pb）可以预先确定淀粉样前体蛋白（APP）及其淀粉样生成β-淀粉样蛋白（Abeta）产品的表达和调控。在这里，我们报道在暴露于Pb的老年（23岁）猴子中，AD相关基因[APP，BACE1（β位APP裂解酶1）]及其转录调节因子（Sp1）的表达升高。作为婴儿。此外，发育中的铅暴露改变了额叶皮层中Abeta染色和淀粉样蛋白斑块的水平，特征和细胞内分布。这些潜在的影响伴随着DNA甲基转移酶活性的降低和对DNA的氧化损伤的增加，表明在早期生命中的表观遗传印迹影响了AD相关基因的表达并促进了DNA损伤和发病机理。这些数据表明，AD的发病机理受早期生命暴露的影响，并为AD的环境触发和发育起源提供了依据。

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