THE ROLE OF CHOROID PLEXUS IN IVIG-INDUCED BETA-AMYLOID CLEARANCE

We have shown that intravenous immunoglobulin (IVIG) contains anti-A beta autoantibodies and IVIG could induce beta amyloid (A beta) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Ab efflux remains unclear. In this study, we used amyloid precursor protein (A beta PP) transgenic mice to investigate if the IVIG could induce efflux of A beta from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic A beta transporter in blood-CSF barrier (BCB); could mediate this clearance process. We currently provide strong evidence to demonstrate that IVIG could reduce brain A beta levels by pulling Ab into the blood system in AbPP transgenic mice. In the mechanistic study, IVIG could induce A beta 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 A beta efflux. Should A beta 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 A beta from the brain through the LRP1 in the BCB. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.