title: A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice.
abstract: Amyloid plaques are a characteristic feature in Alzheimer's disease (AD). A novel non-toxic contrast agent is presented, Gd-DTPA-K6Abeta1-30, which is homologous to Abeta, and allows plaque detection in vivo. microMRI was performed on AD model mice and controls prior to and following intracarotid injection with Gd-DTPA-K6Abeta1-30 in mannitol solution, to transiently open the blood-brain barrier. A gradient echo T2(*)-weighted sequence was used to provide 100 microm isotropic resolution with imaging times of 115 min. The scans were examined with voxel-based analysis (VBA) using statistical parametric mapping, for un-biased quantitative comparison of ligand-injected mice and controls. The results indicate that: (1) Gd-DTPA-K6Abeta1-30 is an effective, non-toxic, ligand for plaque detection when combined with VBA (p< or =0.01-0.001), comparing pre and post-ligand injection scans. (2) Large plaques can be detected without the use of a contrast agent and this detection co-localizes with iron deposition. (3) Smaller, earlier plaques require contrast ligand for MRI visualization. Our ligand when combined with VBA may be useful for following therapeutic approaches targeting amyloid in transgenic mouse models.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. einar.sigurdsson@med.nyu.edu
authors.forename: Einar M
authors.initials: EM
authors.lastname: Sigurdsson
authors.forename: Youssef Z
authors.initials: YZ
authors.lastname: Wadghiri
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Blind
authors.forename: Elin
authors.initials: E
authors.lastname: Knudsen
authors.forename: Ayodeji
authors.initials: A
authors.lastname: Asuni
authors.forename: Henrieta
authors.initials: H
authors.lastname: Scholtzova
authors.forename: Wai H
authors.initials: WH
authors.lastname: Tsui
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: Sadowski
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Turnbull
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media / Q000633:toxicity; D004195:Disease Models, Animal; D005682:Gadolinium; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D015336:Molecular Probe Techniques; D010446:Peptide Fragments; D058225:Plaque, Amyloid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D003287:Contrast Media; D008024:Ligands; C493918:Lys-Lys-Lys-Lys-Lys-Lys-amyloid beta (1-30)-amide; D010446:Peptide Fragments; D005682:Gadolinium