Mouse models are valuable tools for investigating pathogenic mechanisms related to neurodegeneration. For Alzheimer's disease, several animal models have been generated which recapitulate critical aspects of the disease, such as accumulation of Tau aggregates accompanied by neuronal loss and brain atrophy. However, the detailed mechanisms of how these events occur are still not fully understood. To determine the temporal relationship between Tau pathology and neuronal loss, we used JNPL3 transgenic mice, which express human Tau with P301L mutation. JNPL3 mice develop Tau neurofibrillary tangles around 6 months of age followed by motor and behavioral abnormalities by 10 months. Magnetic resonance imaging (MRI) analyses were performed on WT and JNPL3 animals at 5, 10 and 15 months to measure the volume of selected brain areas. Furthermore, we used diffusion tensor imaging (DTI) MRI protocol to investigate alterations of the integrity of white matter. We found that brain atrophy was already discernible in JNPL3 mice at 5 months in the cortex, striatum and hippocampus and worsened over time. We also detected differences in DTI parameters in the corpus callosum and fimbria of JNPL3 mice at 5 months, suggesting that both grey as well as white matter degeneration occur as early as 5 months in JNPL3 mice, preceding motor and cognitive dysfunctions, assessed by rotarod and radial arm water maze. We propose that these non-invasive MRI techniques offer insight into pathologic mechanisms underpinning Alzheimer's disease that may be important when evaluating therapeutics targeting one of more of these processes.