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-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.
Sigurdsson
Einar M
EM
Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. einar.sigurdsson@med.nyu.edu
Wadghiri
Youssef Z
YZ
Mosconi
Lisa
L
Blind
Jeffrey A
JA
Knudsen
Elin
E
Asuni
Ayodeji
A
Scholtzova
Henrieta
H
Tsui
Wai H
WH
Li
Yongsheng
Y
Sadowski
Martin
M
Turnbull
Daniel H
DH
de Leon
Mony J
MJ
Wisniewski
Thomas
T
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*
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