The overall goal of this project is to examine usefulness of magnetic resonance microimaging (MRM) for the characterization of macroscopic neuroanatomy of mouse models of Alzheimer's disease. The mouse models of AD is a powerful step for better understanding of pathogenic mechanisms and in the development of new therapeutic strategies. In these mouse models, the primary indices of pathology are the amyloid plaques. However, the temporal and spatial pattern of amyloid deposition is not well characterized in the various mouse models of AD. Moreover, it is currently not known whether different transgenic mouse models of amyloid deposition shows similar pattern of amyloid deposition. The traditional analyses of amyloid deposition and other anatomical analyses such as volume measurements based on the serial histology sections, are not ideal for efficiently following the macroscopic evolution of the disease nor analysis of large number of mice required for screening the effects of therapeutic measures. In this study, we will apply the MRM to the characterization of mouse models of AD and other mouse models of neurodegenerative diseases.
Aim 1 is to compare the three-dimensional distribution of amyloid plaques and changes in brain volumes of two transgenic mouse models of AD using ex vivo brains. Hypothesis: The MRM can efficiently characterize three-dimensional plaque distribution and brain volume changes.
Aim 2 : To develop in vivo MRM to replicate the study in Aim 1 in living animals. Hypothesis: The amyloid plaque detection and volume measurements can be achieved in vivo. To confirm these hypotheses, 2 mouse strains of the AD model will be studied at 4 different ages. ? ?
| Chuang, Nelson; Mori, Susumu; Yamamoto, Akira et al. (2011) An MRI-based atlas and database of the developing mouse brain. Neuroimage 54:80-9 |
| Aggarwal, M; Zhang, J; Miller, M I et al. (2009) Magnetic resonance imaging and micro-computed tomography combined atlas of developing and adult mouse brains for stereotaxic surgery. Neuroscience 162:1339-50 |
