Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice.
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.
Wilcock
Donna M
DM
Department of Pharmacology and Molecular Therapeutics, University of South Florida, Tampa, Florida 33612, USA.
Alamed
Jennifer
J
Gottschall
Paul E
PE
Grimm
Jan
J
Rosenthal
Arnon
A
Pons
Jaume
J
Ronan
Victoria
V
Symmonds
Keisha
K
Gordon
Marcia N
MN
Morgan
Dave
D
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002539:Cerebral Arterial Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006031:Glycosylation; D007167:Immunotherapy / Q000379:methods; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies