title: Targeting the amyloid-β antibody in the brain tissue of a mouse model of Alzheimer's disease.
abstract: Alzheimer's disease is a neurodegenerative disease characterized pathologically by amyloid-β (Aβ) aggregates in the brain. Notwithstanding many promising therapeutics that are under development, early diagnosis of Alzheimer's disease is limited. By targeting the Aβ aggregates, diagnosis can be improved and disease progression reduced. Molecular imaging using monoclonal antibodies to target specific isoforms of Aβ aggregates offer increased specificity in comparison to conventional imaging tracers; however, antibodies that are widely used in histology do not necessarily show similar binding in a dynamic in vivo environment. In this study, the diffusion and binding were studied of a classical monoclonal antibody, 6E10, in the brain of the TgCRND8 mouse model of AD. After intracranial injection of fluorescent 6E10, we observed broad and rapid labelling of Aβ deposits in the cortex and corpus callosum within 4h. Aβ plaques were detected up to 2.5mm away from the injection site in TgCRND8 mice and not in wild type mice at all, demonstrating specificity of binding. The apparent diffusivity and elimination constant of the anti-Aβ antibody were found to be independent of both the age of the animal and the accumulation of Aβ in the extracellular space, suggesting broad applicability of this targeting molecule. Mathematical modelling of the diffusion profiles of the anti-Aβ antibody in the brain parenchyma provides insights into the utility of antibodies as molecular imaging tools and targeted therapeutics.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: McLean
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cooke
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Fraser
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal