Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Neurosci Lett. 2011 Feb 18;490(1):16-20. doi: 10.1016/j.neulet.2010.12.017. Epub 2010 Dec 16.
Lead (Pb) is an environmental factor suspected of contributing to neurodegenerative diseases such as Alzheimer's disease (AD). In AD, it has been postulated that increased production and/or decreased metabolism/clearance of β-amyloid (Aβ) may lead to amyloid plaque deposition as well as a cascade of other neuropathological changes. It has been suggested that Pb exposure may be associated with AD-like pathology and severe memory deficits in humans. Therefore, we investigated whether Pb exposure could induce Aβ accumulation in the brain. In this study, we demonstrated that acute Pb treatments lead to increased levels of Aβ in the cerebrospinal fluid (CSF) and brain tissues. Interestingly, Pb treatments did not affect Aβ production in brain neurons. Furthermore, Pb treatments significantly decreased LRP1 protein expression in the choroid plexus (CP). Our results suggest disrupted LRP1-mediated transport of Aβ in this region may be responsible for the Aβ accumulation in brain.
铅（Pb）是一种环境因素，被怀疑与阿尔茨海默病（AD）等神经退行性疾病有关。在 AD 中，有人假设β-淀粉样蛋白（Aβ）的产生增加和/或代谢/清除减少可能导致淀粉样斑块沉积以及一系列其他神经病理学变化。有人认为 Pb 暴露可能与 AD 样病理学和人类严重的记忆缺陷有关。因此，我们研究了 Pb 暴露是否会导致大脑中 Aβ的积累。在这项研究中，我们证明急性 Pb 处理会导致脑脊液（CSF）和脑组织中 Aβ水平升高。有趣的是，Pb 处理不会影响脑神经元中 Aβ的产生。此外，Pb 处理显著降低脉络丛（CP）中的 LRP1 蛋白表达。我们的结果表明，该区域 LRP1 介导的 Aβ转运的破坏可能是导致大脑中 Aβ积累的原因。
