title: Gadolinium-staining reveals amyloid plaques in the brain of Alzheimer's transgenic mice.
abstract: Detection of amyloid plaques in the brain by in vivo neuroimaging is a very promising biomarker approach for early diagnosis of Alzheimer's disease (AD) and evaluation of therapeutic efficacy. Here we describe a new method to detect amyloid plaques by in vivo magnetic resonance imaging (MRI) based on the intracerebroventricular injection of a nontargeted gadolinium (Gd)-based contrast agent, which rapidly diffuses throughout the brain and increases the signal and contrast of magnetic resonance (MR) images by shortening the T1 relaxation time. This gain in image sensitivity after in vitro and in vivo Gd staining significantly improves the detection and resolution of individual amyloid plaques in the cortex and hippocampus of AD transgenic mice. The improved image resolution is sensitive enough to demonstrate an age-dependent increase of amyloid plaque load and a good correlation between the amyloid load measured by μMRI and histology. These results provide the first demonstration that nontargeted Gd staining can enhance the detection of amyloid plaques to follow the progression of AD and to evaluate the activity of amyloid-lowering therapeutic strategies in longitudinal studies.
authors.affiliation: Sanofi-aventis, Aging Therapeutic Strategic Unit, Chilly-Mazarin, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Petiet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Santin
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wiggins
authors.forename: Fanny
authors.initials: F
authors.lastname: Petit
authors.forename: Diane
authors.initials: D
authors.lastname: Houitte
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.forename: Jesus
authors.initials: J
authors.lastname: Benavides
authors.forename: Thomas
authors.initials: T
authors.lastname: Debeir
authors.forename: Thomas
authors.initials: T
authors.lastname: Rooney
authors.forename: Marc
authors.initials: M
authors.lastname: Dhenain
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods; D058225:Plaque, Amyloid / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005682:Gadolinium