MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease

• Published in: Magnetic resonance in medicine 2004-04, Vol.51 (4), p.794-798
• Main Authors: Helpern, Joseph A., Lee, Sang-Pil, Falangola, Maria F., Dyakin, Victor V., Bogart, Adam, Ardekani, Babak, Duff, Karen, Branch, Craig, Wisniewski, Thomas, de Leon, Mony J., Wolf, Oliver, O'Shea, Jacqueline, Nixon, Ralph A.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - diagnosis; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; Brain - pathology; Corpus Callosum - pathology; Disease Models, Animal; Gyrus Cinguli - pathology; Hippocampus - pathology; Magnetic Resonance Imaging; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Transgenic; MRI; Mutation - genetics; Presenilin-1; transgenic mice; β-amyloid
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.20038

The cerebral deposition of amyloid β‐peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high‐field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1) transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of β‐amyloid in several brain regions, starting from 10 weeks of age; 2) transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Aβ‐peptide without β‐amyloid deposition; and 3) nontransgenic (NTg) littermates as controls. The transverse relaxation time T2, an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS‐APP mice compared to NTg. No differences in T1 values or proton density were detected between any groups of mice. These results indicate that T2 may be a sensitive marker of abnormalities in this transgenic mouse model of AD. Magn Reson Med 51:794–798, 2004. © 2004 Wiley‐Liss, Inc.