Deglycosylated Anti-Aβ Antibody Dose–Response Effects on Pathology and Memory in APP Transgenic Mice

Journal of Neuroimmune Pharmacology - Tập 3 - Trang 187-197 - 2008
Rachel A. Karlnoski1, Arnon Rosenthal2, Jennifer Alamed1, Victoria Ronan1, Marcia N. Gordon1, Paul E. Gottschall1, Jan Grimm2, Jaume Pons2, Dave Morgan1
1School of Basic Biomedical Sciences, Department of Molecular Pharmacology and Physiology, Alzheimer’s Research Laboratory, University of South Florida, Tampa, USA
2Rinat Labs, Pfizer Inc., South San Francisco, USA

Tóm tắt

Anti-Aβ 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 Fcγ 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 Aβ clearance, possibly by saturating the FcRn antibody transporter.

Tài liệu tham khảo

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