Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice.
Anti-Abeta antibody administration to amyloid-depositing transgenic mice can reverse amyloid pathology and restore memory function. However, in old mice, these treatments also increase vascular leakage and promote formation of vascular amyloid deposits. Deglycosylated antibodies with reduced affinity for Fcgamma receptors and complement are associated with reduced vascular amyloid and microhemorrhage while retaining amyloid-clearing and memory-enhancing properties of native intact antibodies. In the current experiment, we investigated the effect of 3, 10, or 30 mg/kg of deglycosylated antibody (D-2H6) on amyloid pathology and cognitive behavior in old Tg2576 mice. We found that low doses of deglycosylated antibody appear more efficacious than higher doses in reducing pathology and memory loss in amyloid precursor protein (APP) transgenic mice. These data suggest that excess antibody unbound to antigen can interfere with antibody-mediated Abeta clearance, possibly by saturating the FcRn antibody transporter.
Karlnoski
Rachel A
RA
School of Basic Biomedical Sciences, Department of Molecular Pharmacology and Physiology, Alzheimer's Research Laboratory, University of South Florida, 12901 Bruce B Downs Blvd, MDC Box 8, Tampa, FL 33612-4799, USA. rkarlnos@hsc.usf.edu
Rosenthal
Arnon
A
Alamed
Jennifer
J
Ronan
Victoria
V
Gordon
Marcia N
MN
Gottschall
Paul E
PE
Grimm
Jan
J
Pons
Jaume
J
Morgan
Dave
D
D000375:Aging / Q000235:genetics; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004306:Dose-Response Relationship, Immunologic; D006031:Glycosylation; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies