Passive Immunization of the Aβ42(43) C-Terminal-Specific Antibody BC05 in a Mouse Model of Alzheimer's Disease

Background: Over the past few years, amyloid beta protein (A beta) 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 A beta 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 A beta 42(43), on the clearance of brain A beta 42(43). Method: The BC05 antibody was injected into the peritoneal cavity of Tg2576 transgenic mice expressing beta APP(KM670/671NL) once a week from 3 to 12 months of age. Results: BC05 caused a selective 44-fold increase in plasma A beta 42(43) and a significant increase in brain soluble A beta 42(43), showing a 156% difference. Brain insoluble A beta 40 and A beta 42(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 A beta 42(43) soluble within the brain and inhibit the insoluble deposition of A beta 40 and A beta 42(43). By analyzing the mechanism of the elevation of soluble A beta 42(43) after passive immunization of BC05, safer and more effective methods of immunotherapy for Alzheimer's disease might be developed. Copyright (c) 2005 S. Karger AG, Basel