The F(ab)'2 fragment of an Abeta-specific monoclonal antibody reduces Abeta deposits in the brain.
This work examines whether administering the F(ab' )2 fragment of an IgG1 monoclonal antibody (mAb) targeting the N-terminal 1-13 amino acids of the beta-amyloid peptide (Abeta mAb) reduces amyloid deposition in Alzheimer's disease (AD). The F(ab')2 fragment was injected intraperitoneally or intracranially into Tg2576 mice, a murine model of human AD. Both routes of administration significantly reduced Abeta plaque formation in the brain, as determined immunohistochemically and by monitoring levels of Abeta1-40 and Abeta1-42 peptide. Use of the F(ab')2 fragment significantly reduced phagocytic infiltration in the CNS when compared to intact mAb. Since IgG1 Abs do not fix complement, these findings suggest that effective in vivo clearance of amyloid deposits can be achieved without stimulation of FcR-reactive phagocytes or activation of the complement cascade.
Tamura
Yuichi
Y
Nichiiko Pharmaceutical, Co., Ltd, Toyama, Japan.
Hamajima
Kenji
K
Matsui
Kiyohiko
K
Yanoma
Shunsuke
S
Narita
Masato
M
Tajima
Nobuyoshii
N
Xin
Ke-Qin
KQ
Klinman
Dennis
D
Okuda
Kenji
K
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003165:Complement System Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects / Q000502:physiology; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D003165:Complement System Proteins