title: The role of choroid plexus in IVIG-induced beta-amyloid clearance.
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.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202.
authors.forename: Huiying
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202.|Department of General Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, IN, 47907.
authors.forename: Wendy
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202.
authors.forename: Eileen
authors.initials: E
authors.lastname: Du
authors.affiliation: Department of Neurology, Philipps University Marburg, Marburg, Germary.
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, IN, 47907.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202.|School of Health Sciences, Purdue University, West Lafayette, IN, 47907.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
mesh_terms: D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D034741:RNA, Small Interfering; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins
keywords: Aβ clearance; IVIG; LRP1; choroid plexus
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