Passive immunization of the Abeta42(43) C-terminal-specific antibody BC05 in a mouse model of Alzheimer's disease.
BACKGROUND
Over the past few years, amyloid beta protein (Abeta) vaccination has become one of the most effective treatments for Alzheimer's disease. However, the appearance of severe side effects during clinical trials has highlighted the need for improved safety and efficacy. Although antibodies directed against the amino (N)-termini of Abeta are highly effective for passive immunization, a substantial risk of inducing cerebral hemorrhage has been documented.


OBJECTIVE
We investigated the effect of the administration of BC05, which was the first antibody developed against the carboxyl (C)-termini of Abeta42(43), on the clearance of brain Abeta42(43).


METHODS
The BC05 antibody was injected into the peritoneal cavity of Tg2576 transgenic mice expressing betaAPP(KM670/671NL) once a week from 3 to 12 months of age.


RESULTS
BC05 caused a selective 44-fold increase in plasma Abeta42(43) and a significant increase in brain soluble Abeta42(43), showing a 156% difference. Brain insoluble Abeta40 and Abeta42(43) levels were decreased by 27.3 and 31.5%, respectively. A reduction in the number of BAN50-labeled plaques was observed.


CONCLUSIONS
BC05 might render Abeta42(43) soluble within the brain and inhibit the insoluble deposition of Abeta40 and Abeta42(43). By analyzing the mechanism of the elevation of soluble Abeta42(43) after passive immunization of BC05, safer and more effective methods of immunotherapy for Alzheimer's disease might be developed.
Asami-Odaka
Asano
A
Takeda Pharmaceutical Co., Ltd., Pharmacology Research Laboratories, I, Osaka, Japan. Asami_Asano@takeda.co.jp
Obayashi-Adachi
Yuka
Y
Matsumoto
Yoshio
Y
Takahashi
Hideki
H
Fukumoto
Hiroaki
H
Horiguchi
Takashi
T
Suzuki
Nobuhiro
N
Shoji
Mikio
M
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000737:chemistry / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000097:blood* / Q000737:chemistry / Q000276:immunology*; D017434:Protein Structure, Tertiary / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)