A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinical symptoms, efforts to detect brain changes early could significantly enhance our ability to diagnose AD sooner. Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude, orientation, and anisotropy of the diffusion of water in tissues, has been used to infer neuropathological changes in vivo. Its utility in AD, however, is still under investigation. The current study used DTI to examine brain regions susceptible to AD-related pathology; the cerebral cortex, entorhinal cortex, and hippocampus, in 12-14-month-old 3xTg AD mice that possess both Aβ plaques and neurofibrillary tangles. Mean diffusivity did not differ between 3xTg and control mice in any region. Decreased fractional anisotropy (p