title: Lead exposure increases levels of β-amyloid in the brain and CSF and inhibits LRP1 expression in APP transgenic mice.
abstract: 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.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Huiying
authors.initials: H
authors.lastname: Gu
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Monnot
authors.forename: Christine V
authors.initials: CV
authors.lastname: Fontanilla
authors.forename: Mamta
authors.initials: M
authors.lastname: Behl
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007854:Lead / Q000494:pharmacology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects; D010649:Phenylalanine / Q000235:genetics; D058225:Plaque, Amyloid / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014633:Valine / Q000235:genetics
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D007854:Lead; D010649:Phenylalanine; D014633:Valine