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The Journal of Neuroscience, May 17, 2006, 26(20):5340-5346; doi:10.1523/JNEUROSCI.0695-06.2006

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Neurobiology of Disease
Deglycosylated Anti-Amyloid- Antibodies Eliminate Cognitive Deficits and Reduce Parenchymal Amyloid with Minimal Vascular Consequences in Aged Amyloid Precursor Protein Transgenic Mice

Donna M. Wilcock,¹ Jennifer Alamed,¹ Paul E. Gottschall,¹ Jan Grimm,² Arnon Rosenthal,² Jaume Pons,² Victoria Ronan,¹ Keisha Symmonds,¹ Marcia N. Gordon,¹ and Dave Morgan¹

¹Alzheimer’s Research Laboratory, Department of Pharmacology and Molecular Therapeutics, University of South Florida, Tampa, Florida 33612, and ²Rinat Neurosciences Corporation, South San Francisco, California 94080

Correspondence should be addressed to Dave Morgan, Department of Pharmacology and Molecular Therapeutics, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC Box 9, Tampa, FL 33612. Email: dmorgan{at}hsc.usf.edu

Systemic administration of anti-amyloid- (A) antibodies results in reduced parenchymal amyloid but increased vascular amyloid and microhemorrhage in amyloid precursor protein (APP) transgenic mice. Here, we evaluate the effects of reducing effector interactions of the antibody via deglycosylation. Mice aged 20 months were treated weekly for 4 months and tested behaviorally before they were killed. APP transgenic mice receiving either anti-A (2H6) or deglycosylated anti-A (de-2H6) showed significant improvement in radial arm water maze performance compared with mice receiving a control antibody. Both groups receiving anti-A antibodies showed significant reductions in total A immunochemistry and Congo red. Significantly fewer vascular amyloid deposits and microhemorrhages were observed in mice administered the de-2H6 antibody compared with those receiving unmodified 2H6 antibody. Deglycosylated anti-A antibodies may be preferable to unmodified IgG because they retain the cognition-enhancing and amyloid-reducing properties of anti-A immunotherapy, while greatly attenuating the increased vascular amyloid deposition and microhemorrhage observed with unmodified IgG.

Key words: immunotherapy; microglia; microhemorrhage; CAA; Alzheimer’s; vaccination

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Received Feb. 16, 2006; revised April 5, 2006; accepted April 12, 2006.

Correspondence should be addressed to Dave Morgan, Department of Pharmacology and Molecular Therapeutics, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC Box 9, Tampa, FL 33612. Email: dmorgan{at}hsc.usf.edu

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