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Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice.
J Neurosci. 2006 May 17; 26(20):5340-6.JN

Abstract

Systemic administration of anti-amyloid-beta (Abeta) 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-Abeta (2H6) or deglycosylated anti-Abeta (de-2H6) showed significant improvement in radial arm water maze performance compared with mice receiving a control antibody. Both groups receiving anti-Abeta antibodies showed significant reductions in total Abeta 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-Abeta antibodies may be preferable to unmodified IgG because they retain the cognition-enhancing and amyloid-reducing properties of anti-Abeta immunotherapy, while greatly attenuating the increased vascular amyloid deposition and microhemorrhage observed with unmodified IgG.

Authors+Show Affiliations

Department of Pharmacology and Molecular Therapeutics, University of South Florida, Tampa, Florida 33612, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16707786

Citation

Wilcock, Donna M., et al. "Deglycosylated Anti-amyloid-beta Antibodies Eliminate Cognitive Deficits and Reduce Parenchymal Amyloid With Minimal Vascular Consequences in Aged Amyloid Precursor Protein Transgenic Mice." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 26, no. 20, 2006, pp. 5340-6.
Wilcock DM, Alamed J, Gottschall PE, et al. Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. J Neurosci. 2006;26(20):5340-6.
Wilcock, D. M., Alamed, J., Gottschall, P. E., Grimm, J., Rosenthal, A., Pons, J., Ronan, V., Symmonds, K., Gordon, M. N., & Morgan, D. (2006). Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 26(20), 5340-6.
Wilcock DM, et al. Deglycosylated Anti-amyloid-beta Antibodies Eliminate Cognitive Deficits and Reduce Parenchymal Amyloid With Minimal Vascular Consequences in Aged Amyloid Precursor Protein Transgenic Mice. J Neurosci. 2006 May 17;26(20):5340-6. PubMed PMID: 16707786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. AU - Wilcock,Donna M, AU - Alamed,Jennifer, AU - Gottschall,Paul E, AU - Grimm,Jan, AU - Rosenthal,Arnon, AU - Pons,Jaume, AU - Ronan,Victoria, AU - Symmonds,Keisha, AU - Gordon,Marcia N, AU - Morgan,Dave, PY - 2006/5/19/pubmed PY - 2006/6/9/medline PY - 2006/5/19/entrez SP - 5340 EP - 6 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 26 IS - 20 N2 - Systemic administration of anti-amyloid-beta (Abeta) 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-Abeta (2H6) or deglycosylated anti-Abeta (de-2H6) showed significant improvement in radial arm water maze performance compared with mice receiving a control antibody. Both groups receiving anti-Abeta antibodies showed significant reductions in total Abeta 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-Abeta antibodies may be preferable to unmodified IgG because they retain the cognition-enhancing and amyloid-reducing properties of anti-Abeta immunotherapy, while greatly attenuating the increased vascular amyloid deposition and microhemorrhage observed with unmodified IgG. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/16707786/Deglycosylated_anti_amyloid_beta_antibodies_eliminate_cognitive_deficits_and_reduce_parenchymal_amyloid_with_minimal_vascular_consequences_in_aged_amyloid_precursor_protein_transgenic_mice_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=16707786 DB - PRIME DP - Unbound Medicine ER -