Antibody against C-terminal Abeta selectively elevates plasma Abeta

• Published in: Neuroreport Vol. 18; no. 3; p. 293
• Main Authors: Gray, Audrey J, Sakaguchi, Gaku, Shiratori, Chiharu, Becker, Amanda G, LaFrancois, John, Aisen, Paul S, Duff, Karen, Matsuoka, Yasuji
• Format: Journal Article
• Language: English
• Published: England 12.02.2007
• Subjects: Alzheimer Disease - immunology; Alzheimer Disease - metabolism; Alzheimer Disease - therapy; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - immunology; Animals; Antibodies - pharmacology; Antibodies - therapeutic use; Brain - immunology; Brain - metabolism; Brain - physiopathology; Chemotaxis - immunology; Disease Models, Animal; Humans; Immunotherapy - methods; Male; Mice; Mice, Transgenic; Microglia - immunology; Peptide Fragments - immunology; Phagocytosis - immunology; Plaque, Amyloid - immunology; Plaque, Amyloid - metabolism; Protein Structure, Tertiary - physiology; Treatment Outcome
• ISSN: 0959-4965
• DOI: 10.1097/WNR.0b013e3280148e76

Accumulation of amyloid beta in the brain is a pathological hallmark of Alzheimer's disease, and the reduction of amyloid beta has been proposed as a primary therapeutic target. Mice immunized against amyloid beta and mice infused with anti-amyloid beta antibody (active and passive immunization, respectively) have reduced brain amyloid beta levels, and two mechanisms have been proposed: microglial phagocytosis in the brain and enhancement of amyloid beta efflux by antibodies present in the periphery (sequestration). The optimal antibody for microglial phagocytosis has been shown to be N-terminal-specific antibody; however, the potency of C-terminal-specific antibody in sequestration remains unclear. In this study, we found that anti-amyloid beta 40-specific antibody induces amyloid beta sequestration. These results indicate that C-terminal antibodies may be useful in amyloid beta sequestration therapy.