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
Date
05/19/2006Pubmed ID
16707786Pubmed Central ID
PMC6675288DOI
10.1523/JNEUROSCI.0695-06.2006Scopus ID
2-s2.0-33745001453 (requires institutional sign-in at Scopus site) 147 CitationsAbstract
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.
Author List
Wilcock DM, Alamed J, Gottschall PE, Grimm J, Rosenthal A, Pons J, Ronan V, Symmonds K, Gordon MN, Morgan DAuthor
Victoria Ronan MBBS Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgingAlzheimer Disease
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Animals
Antibodies
Blood Vessels
Brain
Cerebral Arterial Diseases
Cognition Disorders
Disease Models, Animal
Down-Regulation
Glycosylation
Immunotherapy
Maze Learning
Memory Disorders
Mice
Mice, Transgenic
Plaque, Amyloid
Treatment Outcome