title: Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model.
abstract: We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species.
authors.affiliation: Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
authors.forename: Jean-Cosme
authors.initials: JC
authors.lastname: Dodart
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Bales
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Gannon
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.forename: Ronald B
authors.initials: RB
authors.lastname: DeMattos
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathis
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: DeLong
authors.forename: Su
authors.initials: S
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000097:blood / Q000134:cerebrospinal fluid; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007116:Immunization, Passive; D007167:Immunotherapy; D007858:Learning / Q000187:drug effects; D008569:Memory Disorders / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex