In this study, we assessed the evolution of diffusion MRI (dMRI) derived markers from different white matter models as progressive neurodegeneration occurs in transgenic Alzheimer rats (TgF344-AD) at 10, 15 and 24 months. We compared biomarkers reconstructed from Diffusion Tensor Imaging (DTI), Neurite Orientation Dispersion and Density Imaging (NODDI) and Mean Apparent Propagator (MAP)-MRI in the hippocampus, cingulate cortex and corpus callosum using multi-shell dMRI. We found that NODDI's dispersion and MAP-MRI's anisotropy markers consistently changed over time, possibly indicating that these measures are sensitive to age-dependent neuronal demise due to amyloid accumulation. Conversely, we found that DTI's mean diffu-sivity, NODDI's isotropic volume fraction and MAP-MRI's restriction-related metrics all followed a two-step progression from 10 to 15 months, and from 15 to 24 months. This two-step pattern might be linked with a neuroinflammatory response that may be occuring prior to, or during microstructural breakdown. Using our approach, we are able to provide for the first time-preliminary and valuable insight on relevant biomarkers that may directly describe the underlying pathophysiology in Alzheimer's disease.