Catalytic antibodies to amyloid β peptide in defense against Alzheimer disease

Immunoglobulins (Igs) that bind amyloid beta peptide (A beta) are under clinical trials for immunotherapy of Alzheimer disease (AD). We have identified IgMs and recombinant Ig fragments that hydrolyze A beta. Hydrolysis of peripheral A beta by the IgMs may induce increased A beta release from the brain. The catalytic IgMs are increased in AD patients, presumably reflecting a protective autoimmune response. Reduced A beta aggregation and neurotoxicity attributable to the catalytic function were evident. These findings provide a foundation for development of catalytic Igs for AD immunotherapy. (C) 2008 Elsevier B.V. All rights reserved.