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

Huiying Gu, Xing Wei, Andrew D. Monnot, Christine V. Fontanilla, Mamta Behl, Martin Farlow, Wei Zheng, Yansheng Du

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)16-20
Number of pages5
JournalNeuroscience Letters
Volume490
Issue number1
DOIs
StatePublished - Feb 18 2011

Fingerprint

Amyloid
Transgenic Mice
Cerebrospinal Fluid
Alzheimer Disease
Brain
Choroid Plexus
Amyloid Plaques
Memory Disorders
Neurodegenerative Diseases
Pathology
Neurons
Lead
Proteins

Keywords

  • β-Amyloid
  • Alzheimer's disease
  • APP transgenic mice
  • Choroid plexus
  • Lead
  • LRP1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lead exposure increases levels of β-amyloid in the brain and CSF and inhibits LRP1 expression in APP transgenic mice. / Gu, Huiying; Wei, Xing; Monnot, Andrew D.; Fontanilla, Christine V.; Behl, Mamta; Farlow, Martin; Zheng, Wei; Du, Yansheng.

In: Neuroscience Letters, Vol. 490, No. 1, 18.02.2011, p. 16-20.

Research output: Contribution to journalArticle

Gu, Huiying ; Wei, Xing ; Monnot, Andrew D. ; Fontanilla, Christine V. ; Behl, Mamta ; Farlow, Martin ; Zheng, Wei ; Du, Yansheng. / Lead exposure increases levels of β-amyloid in the brain and CSF and inhibits LRP1 expression in APP transgenic mice. In: Neuroscience Letters. 2011 ; Vol. 490, No. 1. pp. 16-20.
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