Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model.

TitleImmunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model.
Publication TypeJournal Article
Year of Publication2002
AuthorsDodart J-C, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM, Paul SM
JournalNat Neurosci
Volume5
Issue5
Pagination452-7
Date Published2002 May
ISSN1097-6256
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Antibodies, Monoclonal, Antigen-Antibody Complex, Behavior, Animal, Brain, Disease Models, Animal, Dose-Response Relationship, Drug, Immunization, Passive, Immunotherapy, Learning, Memory Disorders, Mice, Mice, Transgenic, Recognition (Psychology)
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.

DOI10.1038/nn842
Alternate JournalNat. Neurosci.
PubMed ID11941374