Lead exposure increases levels of β-amyloid in the brain and CSF and inhibits LRP1 expression in APP transgenic mice

NEUROSCIENCE LETTERS

卷:490

Article

Gu, Huiying¹  Wei, Xing¹  Monnot, Andrew D.²  Fontanilla, Christine V.¹  Behl, Mamta²  Farlow, Martin R.¹  Zheng, Wei²  Du, Yansheng^1,2 

[1] Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA

[2] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA

关键词: Lead;    Alzheimer's disease;    beta-Amyloid;    LRP1;    Choroid plexus;    APP transgenic mice;   

DOI  :  10.1016/j.neulet.2010.12.017

来源: Elsevier

【 摘 要 】

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 beta-amyloid (A beta) 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 A beta accumulation in the brain. In this study, we demonstrated that acute Pb treatments lead to increased levels of A beta in the cerebrospinal fluid (CSF) and brain tissues. Interestingly, Pb treatments did not affect A beta 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 A beta in this region may be responsible for the A beta accumulation in brain. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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