Magnetic resonance imaging for monitoring therapeutic response in a transgenic mouse model of Alzheimer's disease using voxel-based analysis of amyloid plaques.

Abstract

In this study, we have shown the potential of a voxel-based analysis for imaging amyloid plaques and its utility in monitoring therapeutic response in Alzheimer's disease (AD) mice using manganese oxide nanoparticles conjugated with an antibody of Aβ1-40 peptide (HMON-abAβ40). T1-weighted MR brain images of a drug-treated AD group (n=7), a nontreated AD group (n=7), and a wild-type group (n=7) were acquired using a 7.0 T MRI system before (D-1), 24-h (D+1) after, and 72-h (D+3) after injection with an HMON-abAβ40 contrast agent. For the treatment of AD mice, DAPT was injected intramuscularly into AD transgenic mice (50 mg/kg of body weight). For voxel-based analysis, the skull-stripped mouse brain images were spatially normalized, and these voxels' intensities were corrected to reduce voxel intensity differences across scans in different mice. Statistical analysis showed higher normalized MR signal intensity in the frontal cortex and hippocampus of AD mice over wild-type mice on D+1 and D+3 (P<0.01, uncorrected for multiple comparisons). After the treatment of AD mice, the normalized MR signal intensity in the frontal cortex and hippocampus decreased significantly in comparison with nontreated AD mice on D+1 and D+3 (P<0.01, uncorrected for multiple comparisons). These results were confirmed by histological analysis using a thioflavin staining. This unique strategy allows us to detect brain regions that are subjected to amyloid plaque deposition and has the potential for human applications in monitoring therapeutic response for drug development in AD.

• Authors: Jae-Hun Kim, Tae Lin Ha, Geun Ho Im, Jehoon Yang, Sang Won Seo, Julius Juhyun Chung, Sun Young Chae, In Su Lee, Jung Hee Lee
• Journal: Neuroreport (Neuroreport) Vol. 25 Issue 4 Pg. 211-8 (Mar 05 2014) ISSN: 1473-558X [Electronic] England
• PMID: 24518227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Antibodies
• Contrast Media
• Dipeptides
• Enzyme Inhibitors
• Manganese Compounds
• N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
• Oxides
• Peptide Fragments
• amyloid beta-protein (1-40)
• manganese oxide

Topics

• Alzheimer Disease (drug therapy, pathology)
• Amyloid beta-Peptides (immunology)
• Animals
• Antibodies
• Brain (drug effects, pathology)
• Contrast Media
• Dipeptides (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Female
• Frontal Lobe (drug effects, pathology)
• Hippocampus (drug effects, pathology)
• Image Processing, Computer-Assisted
• Magnetic Resonance Imaging (methods)
• Manganese Compounds
• Mice
• Mice, Transgenic
• Nanoparticles
• Oxides
• Peptide Fragments (immunology)
• Plaque, Amyloid (drug therapy, pathology)
• Time Factors