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

• Published in: Neuroscience letters Vol. 490; no. 1; pp. 16 - 20
• Main Authors: Gu, Huiying, Wei, Xing, Monnot, Andrew D., Fontanilla, Christine V., Behl, Mamta, Farlow, Martin R., Zheng, Wei, Du, Yansheng
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 18.02.2011; Elsevier
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid precursor protein; Animals; APP transgenic mice; beta -Amyloid; Biological and medical sciences; Brain; Brain - anatomy & histology; Brain - drug effects; Brain - metabolism; Cells, Cultured; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrospinal fluid; Choroid plexus; Choroid Plexus - drug effects; Choroid Plexus - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Environmental factors; Enzyme-Linked Immunosorbent Assay - methods; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Humans; Lead; Lead - pharmacology; LRP1; Mass Spectrometry - methods; Medical sciences; Memory; Metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation - genetics; Nervous system; Neurodegenerative diseases; Neurology; Neurons; Neurons - drug effects; Phenylalanine - genetics; Plaque, Amyloid - metabolism; Plaques; Receptors, LDL - metabolism; Transgenic mice; Tumor Suppressor Proteins - metabolism; Valine - genetics; Vertebrates: nervous system and sense organs; β-Amyloid; Choroid plexus; Lead; β-Amyloid; LRP1; Alzheimer's disease; APP transgenic mice; Ependymal organ; Nervous system diseases; Alzheimer disease; Rodentia; Central nervous system; Transgenic animal; Cerebrospinal fluid; Cerebral disorder; Encephalon; Vertebrata; Mammalia; Mouse; β Amyloid protein; Central nervous system disease; Degenerative disease
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.12.017

▶ Pb significantly increased Aβ levels in CSF and hippocampus. ▶ Accumulation of Pb decreased LRP1 protein expression in the choroid plexus. ▶ Pb did not affect Aβ production of cortical and hippocampal neurons. 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.