A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice.

Publication Type	Academic Article
Authors	Sigurdsson E, Wadghiri Y, Mosconi L, Blind J, Knudsen E, Asuni A, Scholtzova H, Tsui W, Li Y, Sadowski M, Turnbull D, de Leon M, Wisniewski T
Journal	Neurobiol Aging
Volume	29
Issue	6
Pagination	836-47
Date Published	02/08/2007
ISSN	1558-1497
Keywords	Alzheimer Disease, Amyloid beta-Peptides, Brain, Disease Models, Animal, Gadolinium, Magnetic Resonance Imaging, Peptide Fragments, Plaque, Amyloid
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.
DOI	10.1016/j.neurobiolaging.2006.12.018
PubMed ID	17291630
PubMed Central ID	PMC2408732