| First Author | Gu H | Year | 2014 |
| Journal | Neuroscience | Volume | 270 |
| Pages | 168-176 | PubMed ID | 24747018 |
| Mgi Jnum | J:210621 | Mgi Id | MGI:5571535 |
| Doi | 10.1016/j.neuroscience.2014.04.011 | Citation | Gu H, et al. (2014) The role of choroid plexus in IVIG-induced beta-amyloid clearance. Neuroscience 270:168-176 |
| abstractText | We have shown that intravenous immunoglobulin (IVIG) contains anti-Abeta autoantibodies and IVIG could induce beta amyloid (Abeta) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Abeta efflux remains unclear. In this study, we used amyloid precursor protein (AbetaPP) transgenic mice to investigate if the IVIG could induce efflux of Abeta from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Abeta transporter in blood-CSF barrier (BCB); could mediate this clearance process. We currently provide strong evidence to demonstrate that IVIG could reduce brain Abeta levels by pulling Abeta into the blood system in AbetaPP transgenic mice. In the mechanistic study, IVIG could induce Abeta 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 Abeta efflux. Should Abeta 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 Abeta from the brain through the LRP1 in the BCB. |
