Human monoclonal antibodies against amyloid-beta from healthy adults

Abstract

Two anti-amyloid-beta human antibody-producing cell lines were established from amyloid-beta (Abeta)-selected lymphocytes from peripheral blood of healthy adults. ELISA and Western blot analysis showed that the monoclonal antibodies bound with high affinity to the 43 amino acid-long amyloid-beta peptide. The antigen epitope of these antibodies encountered within amino acids 1-16 of the amyloid-beta peptide. The antibodies did not bind to several immunoglobulin light chain amyloids (AL) and amylin. One of the monoclonals was tested by immunohistochemistry for the binding to frozen sections of brains derived from patients with Alzheimer's disease. It specifically and intensively stained diffuse and core amyloid-beta plaques; whereas, sections from normal brains were not stained. Concomitant staining with a commercial mouse anti-amyloid-beta monoclonal antibody co-localized with that of the human antibody. Simultaneous staining with the human antibody and Congo red implied that the antibody binds primarily to an early immature form of beta-amyloid. Human monoclonal antibodies, which resemble physiologically normal non-pathogenic and possibly protective antibodies in healthy adults, might be attractive candidates for immune therapy of Alzheimer's disease.