Nature Neuroscience5, 452 - 457 (2002)
Published online: 8 April 2002; | doi:10.1038/nn842
Immunization reverses memory deficits without reducing brain A burden in Alzheimer's disease model
Jean-Cosme Dodart1, Kelly R. Bales1, Kimberley S. Gannon1, Stephen J. Greene1, Ronald B. DeMattos2, Chantal Mathis3, Cynthia A. DeLong1, Su Wu1, Xin Wu1, David M. Holtzman2
& Steven M. Paul1
1
Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
2
Center for the Study of Nervous System Injury, Alzheimer's Disease Research Center, Department of Neurology, Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8111, St. Louis, Missouri 63110, USA
3
CNRS UMR 7521, Université Louis Pasteur, 12 rue Goethe, 67000 Strasbourg, France
We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid -peptide (A), increases plasma concentrations of A and reduces A 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 A burden. We also found that an A/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-A 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 A species.
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