Epitopes described in "Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease."

Article Authors:R B DeMattos; K R Bales; D J Cummins; J C Dodart; S M Paul; D M Holtzman
Article Title:Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease.
Reference Detail
Reference ID:1006196
Abstract:Active immunization with the amyloid beta (A beta) peptide has been shown to decrease brain A beta deposition in transgenic mouse models of Alzheimer's disease and certain peripherally administered anti-A beta antibodies were shown to mimic this effect. In exploring factors that alter A beta metabolism and clearance, we found that a monoclonal antibody (m266) directed against the central domain of A beta was able to bind and completely sequester plasma A beta. Peripheral administration of m266 to PDAPP transgenic mice, in which A beta is generated specifically within the central nervous system (CNS), results in a rapid 1,000-fold increase in plasma A beta, due, in part, to a change in A beta equilibrium between the CNS and plasma. Although peripheral administration of m266 to PDAPP mice markedly reduces A beta deposition, m266 did not bind to A beta deposits in the brain. Thus, m266 appears to reduce brain A beta burden by altering CNS and plasma A beta clearance.
Affiliations:The Center for the Study of Nervous System Injury, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110, USA.
Reference Type:Literature
PubMed ID:11438712
Journal:Proc Natl Acad Sci U S A
Journal Volume:98
Article Pages:8850-5
Journal ISSN:0027-8424
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7fff7d1d;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5e6f3c91;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@58f18406;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5812d388
Article MeSH List:Alzheimer Disease(blood; cerebrospinal fluid; metabolism; pathology); Amyloid beta-Peptides(cerebrospinal fluid; immunology; metabolism); Animals; Antibodies, Monoclonal(administration & dosage; immunology; metabolism); Brain(metabolism); Central Nervous System(metabolism); Disease Models, Animal; Humans; Mice; Mice, Transgenic; Peptide Fragments(cerebrospinal fluid; immunology; metabolism)
Curation Last Updated:2015-01-17 21:46:39