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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
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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Intracerebroventricular amyloid-{beta} antibodies reduce cerebral amyloid angiopathy and associated micro-hemorrhages in aged Tg2576 mice
PNAS,
March 17, 2009;
106(11):
4501 - 4506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Robert, O. Dolezal, L. Waddington, M. K. Hattarki, R. Cappai, C. L. Masters, P. J. Hudson, and K. L. Wark
Engineered antibody intervention strategies for Alzheimer's disease and related dementias by targeting amyloid and toxic oligomers
Protein Eng. Des. Sel.,
March 1, 2009;
22(3):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Rapid Microglial Response Around Amyloid Pathology after Systemic Anti-A{beta} Antibody Administration in PDAPP Mice
J. Neurosci.,
December 24, 2008;
28(52):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Nicolakakis, T. Aboulkassim, B. Ongali, C. Lecrux, P. Fernandes, P. Rosa-Neto, X.-K. Tong, and E. Hamel
Complete Rescue of Cerebrovascular Function in Aged Alzheimer's Disease Transgenic Mice by Antioxidants and Pioglitazone, a Peroxisome Proliferator-Activated Receptor {gamma} Agonist
J. Neurosci.,
September 10, 2008;
28(37):
9287 - 9296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Schroeter, K. Khan, R. Barbour, M. Doan, M. Chen, T. Guido, D. Gill, G. Basi, D. Schenk, P. Seubert, et al.
Immunotherapy Reduces Vascular Amyloid-{beta} in PDAPP Mice
J. Neurosci.,
July 2, 2008;
28(27):
6787 - 6793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Maier, Y. Peng, L. Jiang, T. J. Seabrook, M. C. Carroll, and C. A. Lemere
Complement C3 Deficiency Leads to Accelerated Amyloid {beta} Plaque Deposition and Neurodegeneration and Modulation of the Microglia/Macrophage Phenotype in Amyloid Precursor Protein Transgenic Mice
J. Neurosci.,
June 18, 2008;
28(25):
6333 - 6341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Chen, K. S. Chen, D. Kobayashi, R. Barbour, R. Motter, D. Games, S. J. Martin, and R. G. M. Morris
Active {beta}-Amyloid Immunization Restores Spatial Learning in PDAPP Mice Displaying Very Low Levels of {beta}-Amyloid
J. Neurosci.,
March 7, 2007;
27(10):
2654 - 2662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. V. Nikolic, Y. Bai, D. Obregon, H. Hou, T. Mori, J. Zeng, J. Ehrhart, R. D. Shytle, B. Giunta, D. Morgan, et al.
Transcutaneous beta-amyloid immunization reduces cerebral beta-amyloid deposits without T cell infiltration and microhemorrhage
PNAS,
February 13, 2007;
104(7):
2507 - 2512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Jack Jr, M. Marjanska, T. M. Wengenack, D. A. Reyes, G. L. Curran, J. Lin, G. M. Preboske, J. F. Poduslo, and M. Garwood
Magnetic Resonance Imaging of Alzheimer's Pathology in the Brains of Living Transgenic Mice: A New Tool in Alzheimer's Disease Research
Neuroscientist,
February 1, 2007;
13(1):
38 - 48.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. H. Park, G. A. Widi, D. A. Gimbel, N. Y. Harel, D. H. S. Lee, and S. M. Strittmatter
Subcutaneous Nogo Receptor Removes Brain Amyloid-{beta} and Improves Spatial Memory in Alzheimer's Transgenic Mice
J. Neurosci.,
December 20, 2006;
26(51):
13279 - 13286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. D. Roberson and L. Mucke
100 Years and Counting: Prospects for Defeating Alzheimer's Disease
Science,
November 3, 2006;
314(5800):
781 - 784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
