MRI-based diagnostic marker is desired for recruiting patients with progressive supranuclear palsy (PSP) for clinical trials of tau-targeting therapies. Elastic Net analysis was applied to a set of 144 MRI-VOIs (MR images-volumes of interest) to determine the VOIs useful for discriminating tau-positive PSP from healthy controls. The MRI-PSP score, calculated from the analysis, demonstrated 90.0% and 91.1% accuracy for training and validation data. The PSP rating scale correlated well with the MRI-PSP score. The MRI-PSP score calculated by an unbiased analysis system would be a promising diagnostic marker and can potentially predict disease severity in PSP.