Antibody against C-terminal Abeta selectively elevates plasma Abeta.
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.
Gray
Audrey J
AJ
Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.
Sakaguchi
Gaku
G
Shiratori
Chiharu
C
Becker
Amanda G
AG
LaFrancois
John
J
Aisen
Paul S
PS
Duff
Karen
K
Matsuoka
Yasuji
Y
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002633:Chemotaxis / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D058225:Plaque, Amyloid / Q000276:immunology* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments