Quantitative MRI reveals aging-associated T2 changes in mouse models of Alzheimer's disease.
In this study, we used MRI to analyze quantitative parametric maps of transverse (T(2)) relaxation times in a longitudinal study of transgenic mice expressing mutant forms of amyloid precursor protein (APP), presenilin (PS1), or both (PS/APP), modeling aspects of Alzheimer's disease (AD). The main goal was to characterize the effects of progressive beta-amyloid accumulation and deposition on the biophysical environment of water and to investigate if these measurements would provide early indirect evidence of AD pathological changes in the brains of these mice. Our results demonstrate that at an early age before beta-amyloid deposition, only PS/APP mice show a reduced T(2) in the hippocampus and cortex compared with wild-type non-transgenic (NTg) controls, whereas a statistically significant within-group aging-associated decrease in T(2) values is seen in the cortex and hippocampus of all three transgenic genotypes (APP, PS/APP, and PS) but not in the NTg controls. In addition, for animals older than 12 months, we confirmed our previous report that only the two genotypes that form amyloid plaques (APP and PS/APP) have significantly reduced T(2) values compared with NTg controls. Thus, T(2) changes in these AD models can precede amyloid deposition or even occur in AD models that do not deposit beta-amyloid (PS mice), but are intensified in the presence of amyloid deposition.
Falangola
M F
MF
Center for Advanced Brain Imaging, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. falangola@nki.rfmh.org
Dyakin
V V
VV
Lee
S P
SP
Bogart
A
A
Babb
J S
JS
Duff
K
K
Nixon
R
R
Helpern
J A
JA
D000375:Aging / Q000235:genetics / Q000473:pathology*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice