Digital imaging techniques have found several medical applications in the development of computer aided detection systems, especially in neuroimaging. Recent advances in Diffusion Tensor Imaging (DTI) aim to discover biological markers for the early diagnosis of Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorders. We explore here how different supervised classification models provide a robust support to the diagnosis of AD patients. We use DTI measures, assessing the structural integrity of white matter (WM) fiber tracts, to reveal patterns of disrupted brain connectivity. In particular, we provide a voxel-wise measure of fractional anisotropy (FA) and mean diffusivity (MD), thus identifying the regions of the brain mostly affected by neurodegeneration, and then computing intensity features to feed supervised classification algorithms. In particular, we evaluate the accuracy of discrimination of AD patients from healthy controls (HC) with a dataset of 80 subjects (40 HC, 40 AD), from the Alzheimer’s Disease Neurodegenerative Initiative (ADNI). In this study, we compare three state-of-the-art classification models: Random Forests, Naive Bayes and Support Vector Machines (SVMs). We use a repeated five-fold cross validation framework with nested feature selection to perform a fair comparison between these algorithms and evaluate the information content they provide. Results show that AD patterns are well localized within the brain, thus DTI features can support the AD diagnosis.