Magnetization transfer contrast imaging reveals amyloid pathology in Alzheimer's disease transgenic mice

Abstract

The presence of amyloid plaques in the brain is one of the pathological hallmarks of Alzheimer's disease, which might already be present in the early stage of the disease. Therefore it is important to track amyloid plaques as early as possible. In this paper, we report magnetization transfer contrast magnetic resonance imaging (MTC MRI) as a novel approach to detect amyloid plaques in vivo. Two mice models, APP/PS1 and BRI, developing amyloid pathology were investigated with MTC MRI, T2 relaxation measurements and immunohistochemistry (IHC). MT-ratios of several brain regions were compared to T2-values and correlated with quantitative IHC, revealing amyloid load and gliosis in different brain regions. APP/PS1 mice develop large compact plaques, resembling late stage Alzheimer's disease, while rather small and diffuse plaques are deposited in BRI mice, reflecting early stage of Alzheimer's disease. We found significantly higher MT-ratio's in the brain of APP/PS1 mice as compared to their controls and similar trends in BRI mice. A region based MT-ratio and IHC analysis and correlations between MT-ratios and quantitative IHC indicate amyloid plaques as the main substrate for altered MT-ratios in transgenic animals. We additionally demonstrated the improved sensitivity of MTC MRI to amyloid pathology as compared to traditional T2 relaxation measurements. Our results suggest that MTC MRI reveals extensive, and potentially even early amyloid pathology. Further unraveling the MT-effect of each pathological feature during each stage of AD might indicate MTC MRI as a useful diagnostic technique.