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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

Fingerprint

Choroid Plexus
Intravenous Immunoglobulins
Amyloid
Lipoprotein Receptors
Alzheimer Disease
Amyloid beta-Protein Precursor
Transgenic Mice
Cerebrospinal Fluid
Brain
Proteins
Low Density Lipoprotein Receptor-Related Protein-1
Autoantibodies
Small Interfering RNA
Multiple Sclerosis
Epithelial Cells
Membranes

Keywords

  • Aβ clearance
  • Choroid plexus
  • IVIG
  • LRP1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

The role of choroid plexus in IVIG-induced beta-amyloid clearance. / Gu, H.; Zhong, Z.; Jiang, W.; Du, E.; Dodel, R.; Liu, J.; Farlow, Martin; Zheng, W.; Du, Yansheng.

In: Neuroscience, Vol. 270, 13.06.2014, p. 168-176.

Research output: Contribution to journalArticle

Gu, H. ; Zhong, Z. ; Jiang, W. ; Du, E. ; Dodel, R. ; Liu, J. ; Farlow, Martin ; Zheng, W. ; Du, Yansheng. / The role of choroid plexus in IVIG-induced beta-amyloid clearance. In: Neuroscience. 2014 ; Vol. 270. pp. 168-176.
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