Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model.
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.
Dodart
Jean-Cosme
JC
Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Bales
Kelly R
KR
Gannon
Kimberley S
KS
Greene
Stephen J
SJ
DeMattos
Ronald B
RB
Mathis
Chantal
C
DeLong
Cynthia A
CA
Wu
Su
S
Wu
Xin
X
Holtzman
David M
DM
Paul
Steven M
SM
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
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex