Alzheimer's disease (AD) is a neurodegenerative disease that can be induced by heavy metals such as lead. However, there is limited information on the role of blood-brain barrier (BBB) in lead induced AD-like pathology. This study investigates the potential mechanism of lead exposure aggravating the progression of Alzheimer's disease in mice through the BBB. 200 mg/L and 500 mg/L lead acetate were given to C57BL/6 J and APP/PS1 mice through drinking water from a week before mating, until the offspring were 7-months-old. 8 female juvenile mice in each group were selected for this investigation. Lead exposure increased blood lead concentration which revealed the internal exposure level, accelerated Aβ1-42 deposition in APP/PS1 mouse cortexes and abnormal change in Zonula Occludin-1 (ZO-1) and Claudin-5 protein. It also increased the expression of p-tau in both the C57BL/6 J and APP/PS1 mice, and decreased mRNA and protein expression in low-density lipoprotein receptor (LRP-1). Additionally, it increased the mRNA and protein expression of amyloid beta precursor protein (APP) and beta secretase 1 (BACE-1). The activated astrocytes increased in the brains of APP/PS1 mice, and coalesced around the Aβ1-42 deposition after lead exposure. The main vessels in deutocerebrum were attached with Aβ1-42 deposition. These results offer insight into the mechanism of preventing lead induced AD through cerebrovascular pathways.

中文翻译：

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环境铅暴露通过靶向血脑屏障加剧小鼠阿尔茨海默病的进展

阿尔茨海默病 (AD) 是一种神经退行性疾病，可由铅等重金属诱发。然而，关于血脑屏障 (BBB) 在铅诱导的 AD 样病理中的作用的信息有限。这项研究调查了铅暴露通过 BBB 加剧小鼠阿尔茨海默病进展的潜在机制。C57BL/6 J 和 APP/PS1 小鼠在交配前一周通过饮水给予 200 mg/L 和 500 mg/L 醋酸铅，直到后代 7 个月大。每组选择8只雌性幼鼠进行本次调查。铅暴露会增加血铅浓度，这揭示了内暴露水平，加速了 APP/PS1 小鼠皮层中 Aβ1-42 的沉积以及 Zonula Occludin-1 (ZO-1) 和 Claudin-5 蛋白的异常变化。它还增加了 C57BL/6 J 和 APP/PS1 小鼠中 p-tau 的表达，并降低了低密度脂蛋白受体 (LRP-1) 的 mRNA 和蛋白质表达。此外，它还增加了淀粉样β前体蛋白 (APP) 和 β 分泌酶 1 (BACE-1) 的 mRNA 和蛋白质表达。APP/PS1 小鼠大脑中活化的星形胶质细胞增加，并在铅暴露后聚集在 Aβ1-42 沉积物周围。后脑中的主要血管附着有Aβ1-42沉积。这些结果提供了对通过脑血管通路预防铅诱发 AD 的机制的见解。它增加了淀粉样β前体蛋白（APP）和β分泌酶1（BACE-1）的mRNA和蛋白质表达。APP/PS1 小鼠大脑中活化的星形胶质细胞增加，并在铅暴露后聚集在 Aβ1-42 沉积物周围。后脑中的主要血管附着有Aβ1-42沉积。这些结果提供了对通过脑血管通路预防铅诱发 AD 的机制的见解。它增加了淀粉样β前体蛋白（APP）和β分泌酶1（BACE-1）的mRNA和蛋白质表达。APP/PS1 小鼠大脑中活化的星形胶质细胞增加，并在铅暴露后聚集在 Aβ1-42 沉积物周围。后脑中的主要血管附着有Aβ1-42沉积。这些结果提供了对通过脑血管通路预防铅诱发 AD 的机制的见解。