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

Amyloid plaques are a characteristic feature in Alzheimer's disease (AD). A novel non-toxic contrast agent is presented, Gd-DTPA-K6A beta 1-30, which is homologous to A beta, and allows plaque detection in vivo. mu MRI was performed on AD model mice and controls prior to and following intracarotid injection with Gd-DTPA-K6A beta 1-30 in mannitol solution, to transiently open the blood-brain barrier. A gradient echo T2*-weighted sequence was used to provide 100 mu m 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-K6A beta 1-30 is an effective, non-toxic, ligand for plaque detection when combined with VBA (p <= 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. (C) 2007 Elsevier Inc. All rights reserved.