title: In Vivo Detection of Amyloid Plaques by Gadolinium-Stained MRI Can Be Used to Demonstrate the Efficacy of an Anti-amyloid Immunotherapy.
abstract: Extracellular deposition of β amyloid plaques is an early event associated to Alzheimer's disease. Here, we have used in vivo gadolinium-stained high resolution (29(∗)29(∗)117 μm(3)) magnetic resonance imaging (MRI) to follow-up in a longitudinal way individual amyloid plaques in APP/PS1 mice and evaluate the efficacy of a new immunotherapy (SAR255952) directed against protofibrillar and fibrillary forms of Aβ. APP/PS1 mice were treated for 5 months between the age of 3.5 and 8.5 months. SAR255952 reduced amyloid load in 8.5-months-old animals, but not in 5.5-months animals compared to mice treated with a control antibody (DM4). Histological evaluation confirmed the reduction of amyloid load and revealed a lower density of amyloid plaques in 8.5-months SAR255952-treated animals. The longitudinal follow-up of individual amyloid plaques by MRI revealed that plaques that were visible at 5.5 months were still visible at 8.5 months in both SAR255952 and DM4-treated mice. This suggests that the amyloid load reduction induced by SAR255952 is related to a slowing down in the formation of new plaques rather than to the clearance of already formed plaques.
authors.affiliation: Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, UMR 9199, Neurodegenerative Diseases LaboratoryFontenay-aux-Roses, France; Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut d'Imagerie Biomédicale, MIRCenFontenay-aux-Roses, France.
authors.forename: Mathieu D
authors.initials: MD
authors.lastname: Santin
authors.affiliation: Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, UMR 9199, Neurodegenerative Diseases LaboratoryFontenay-aux-Roses, France; Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut d'Imagerie Biomédicale, MIRCenFontenay-aux-Roses, France.
authors.forename: Michel E
authors.initials: ME
authors.lastname: Vandenberghe
authors.affiliation: Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, UMR 9199, Neurodegenerative Diseases LaboratoryFontenay-aux-Roses, France; Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut d'Imagerie Biomédicale, MIRCenFontenay-aux-Roses, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Herard
authors.affiliation: Sanofi, Neurodegeneration and Pain Unit Chilly-Mazarin, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.affiliation: Sanofi, Neurodegeneration and Pain Unit Chilly-Mazarin, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Sanofi, Chilly-Mazarin France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Debeir
authors.affiliation: Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, UMR 9199, Neurodegenerative Diseases LaboratoryFontenay-aux-Roses, France; Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut d'Imagerie Biomédicale, MIRCenFontenay-aux-Roses, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Delzescaux
authors.affiliation: Sanofi, Neurodegeneration and Pain Unit Chilly-Mazarin, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rooney
authors.affiliation: Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, UMR 9199, Neurodegenerative Diseases LaboratoryFontenay-aux-Roses, France; Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut d'Imagerie Biomédicale, MIRCenFontenay-aux-Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dhenain
keywords: Alzheimer; MRI; amyloid; gadolinium; immunotherapy