The role of choroid plexus in IVIG-induced beta-amyloid clearance

H. Gu, Z. Zhong, W. Jiang, E. Du, R. Dodel, J. Liu, M. R. Farlow, W. Zheng, Y. Du

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We have shown that intravenous immunoglobulin (IVIG) contains anti-Aβ autoantibodies and IVIG could induce beta amyloid (Aβ) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Aβ efflux remains unclear. In this study, we used amyloid precursor protein (AβPP) transgenic mice to investigate if the IVIG could induce efflux of Aβ from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Aβ transporter in blood-CSF barrier (BCB); could mediate this clearance process. We currently provide strong evidence to demonstrate that IVIG could reduce brain Aβ levels by pulling Aβ into the blood system in AβPP transgenic mice. In the mechanistic study, IVIG could induce Aβ efflux through the in vitro BCB membrane formed by cultured BCB epithelial cells. Both receptor-associated protein (RAP; a functional inhibitor of LRP1), and LRP1 siRNA were able to significantly inhibit the Aβ efflux. Should Aβ prove to be the underlying cause of AD, our results strongly suggest that IVIG could be beneficial in the therapy for AD by inducing efflux of Aβ from the brain through the LRP1 in the BCB.

Original languageEnglish (US)
Pages (from-to)168-176
Number of pages9
JournalNeuroscience
Volume270
DOIs
StatePublished - Jun 13 2014

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Keywords

  • Aβ clearance
  • Choroid plexus
  • IVIG
  • LRP1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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