Objective: To determine the regions of white matter (WM) atrophy in corticobasal syndrome (CBS) using different methods of diffusion tensor imaging (DTI) analysis. Background CBS is a clinical syndrome mostly associated with frontotemporal lobar degeneration (FTLD), where gray matter atrophy predominantly encompasses frontal and parietal lobes. Although little is known about the pattern of WM disease in CBS, it is known that tau, the histopathological basis of corticobasal degeneration (CBD), has substantial WM burden. For neurodegenerative diseases, there is no gold standard for MRI-based WM analysis. Here, we compared two user-independent approaches in analyzing WM: tract-specific analysis (TSA) and whole-brain analysis. Both used fractional anisotropy (FA), which is sensitive to the integrity of white matter fiber tracts. Design/Methods: In 11 CBS patients and 35 demographically-matched healthy seniors, we analyzed 30-direction diffusion-weighted images. We extracted FA for each individual subject, and registered the image to a common stereotactic space. For TSA, 11 tracts were segmented from a DTI template, converted to 3D binary structures, and modeled as medial meshes to reflect maximum FA locally. For the whole-brain analysis, images were analyzed in local space, localized to a publicly available probabilistic template (ICDM-DTI-81), and then compared statistically with seniors in SPM8. Results: TSA revealed reduced FA in CBS relative to seniors in right uncinate, arcuate fasciculus, and inferior frontal-occipital fasiculus; and bilateral corpus callosum, corticospinal tract and superior longitudinal fasiculus. Whole-brain analysis also revealed reduced FA relative to seniors in the corpus callosum, corticospinal tract, fornix, inferior longitudinal fasiculus, superior longitudinal fasciculus, inferior frontal-occipital fasiculus, and external capsule. Conclusions: In addition to grey matter atrophy, CBS patients have considerable WM disease. TSA and whole-brain analyses display largely overlapping findings, validating user-independent approaches to DTI analyses of WM disease. Supported by: HD060406, NS44266, NS53488, AG15116, AG17586, AG32953, the Wyncote Foundation, NS065347, DA022807, EB006266, NS045839, EB009321, K25 AG027785. Disclosure: Dr. Chandrasekaren has nothing to disclose. Dr. McMillan has nothing to disclose. Dr. Brun has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Yushkevich has nothing to disclose. Dr. Gee has received research support from Pfizer Inc. Dr. Grossman has nothing to disclose.