Lead Exposure Increases Levels of β-amyloid in the Brain and CSF and Inhibits LRP1 Expression in APP Transgenic Mice

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2010 Dec 21

PMID 21167913

Citations 34

Authors

Huiying Gu

Xing Wei

Andrew D Monnot

Christine V Fontanilla

Mamta Behl

Martin R Farlow

Wei Zheng

Yansheng Du

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Monro O, Mackic J, Yamada S, Segal M, Ghiso J, Maurer C . Substitution at codon 22 reduces clearance of Alzheimer's amyloid-beta peptide from the cerebrospinal fluid and prevents its transport from the central nervous system into blood. Neurobiol Aging. 2002; 23(3):405-12. DOI: 10.1016/s0197-4580(01)00317-7. View

Spies P, Slats D, Sjogren J, Kremer B, Verhey F, Olde Rikkert M . The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer's disease from non-Alzheimer's dementia. Curr Alzheimer Res. 2010; 7(5):470-6. DOI: 10.2174/156720510791383796. View

Kalaria R, Premkumar D, Pax A, Cohen D, Lieberburg I . Production and increased detection of amyloid beta protein and amyloidogenic fragments in brain microvessels, meningeal vessels and choroid plexus in Alzheimer's disease. Brain Res Mol Brain Res. 1996; 35(1-2):58-68. DOI: 10.1016/0169-328x(95)00180-z. View

Ma Z, Wei X, Fontanilla C, Noelker C, Dodel R, Hampel H . Caffeic acid phenethyl ester blocks free radical generation and 6-hydroxydopamine-induced neurotoxicity. Life Sci. 2006; 79(13):1307-11. DOI: 10.1016/j.lfs.2006.03.050. View

Manton W, Kirkpatrick J, Cook J . Does the choroid plexus really protect the brain from lead?. Lancet. 1984; 2(8398):351. DOI: 10.1016/s0140-6736(84)92719-3. View

Shi L, Zheng W . Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro. Hum Exp Toxicol. 2007; 26(3):159-67. PMC: 3980856. DOI: 10.1177/0960327107070560. View

Zawia N . Transcriptional involvement in neurotoxicity. Toxicol Appl Pharmacol. 2003; 190(2):177-88. DOI: 10.1016/s0041-008x(03)00161-3. View

Dawson P, Hofmann S, van der Westhuyzen D, Sudhof T, Brown M, Goldstein J . Sterol-dependent repression of low density lipoprotein receptor promoter mediated by 16-base pair sequence adjacent to binding site for transcription factor Sp1. J Biol Chem. 1988; 263(7):3372-9. View

Shih R, Hu H, Weisskopf M, Schwartz B . Cumulative lead dose and cognitive function in adults: a review of studies that measured both blood lead and bone lead. Environ Health Perspect. 2007; 115(3):483-92. PMC: 1849945. DOI: 10.1289/ehp.9786. View

10.

Hyslop P, Bender M . Methods for sample preparation for direct immunoassay measurement of analytes in tissue homogenates: ELISA assay of amyloid beta-peptides. Curr Protoc Neurosci. 2008; Chapter 7:Unit 7.20. DOI: 10.1002/0471142301.ns0720s18. View

11.

Crossgrove J, Smith E, Zheng W . Macromolecules involved in production and metabolism of beta-amyloid at the brain barriers. Brain Res. 2007; 1138:187-95. PMC: 1950938. DOI: 10.1016/j.brainres.2006.12.022. View

12.

Wang Q, Luo W, Zheng W, Liu Y, Xu H, Zheng G . Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development. Toxicol Appl Pharmacol. 2007; 219(1):33-41. PMC: 3982216. DOI: 10.1016/j.taap.2006.11.035. View

13.

Ogomori K, Kitamoto T, Tateishi J, Sato Y, Suetsugu M, Abe M . Beta-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease. Am J Pathol. 1989; 134(2):243-51. PMC: 1879581. View

14.

Tan J, Ma Z, Han L, Du R, Zhao L, Wei X . Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2005; 289(5):H2265-71. DOI: 10.1152/ajpheart.01106.2004. View

15.

Sasaki A, Iijima M, Yokoo H, Shoji M, Nakazato Y . Human choroid plexus is an uniquely involved area of the brain in amyloidosis: a histochemical, immunohistochemical and ultrastructural study. Brain Res. 1997; 755(2):193-201. DOI: 10.1016/s0006-8993(97)00097-8. View

16.

Crossgrove J, Li G, Zheng W . The choroid plexus removes beta-amyloid from brain cerebrospinal fluid. Exp Biol Med (Maywood). 2005; 230(10):771-6. PMC: 3982214. DOI: 10.1177/153537020523001011. View

17.

Brody D, Magnoni S, Schwetye K, Spinner M, Esparza T, Stocchetti N . Amyloid-beta dynamics correlate with neurological status in the injured human brain. Science. 2008; 321(5893):1221-4. PMC: 2577829. DOI: 10.1126/science.1161591. View

18.

Behl M, Zhang Y, Monnot A, Jiang W, Zheng W . Increased beta-amyloid levels in the choroid plexus following lead exposure and the involvement of low-density lipoprotein receptor protein-1. Toxicol Appl Pharmacol. 2009; 240(2):245-54. PMC: 2753690. DOI: 10.1016/j.taap.2009.05.024. View

19.

Dodart J, Bales K, Johnstone E, Little S, Paul S . Apolipoprotein E alters the processing of the beta-amyloid precursor protein in APP(V717F) transgenic mice. Brain Res. 2002; 955(1-2):191-9. DOI: 10.1016/s0006-8993(02)03437-6. View

20.

Serot J, Foliguet B, Bene M, Faure G . Choroid plexus and ageing in rats: a morphometric and ultrastructural study. Eur J Neurosci. 2001; 14(5):794-8. DOI: 10.1046/j.0953-816x.2001.01693.x. View