Introduction: Tau protein accumulation in the brain is thought to be one of the causes of progressive supranuclear palsy (PSP). The glymphatic system was discovered a decade ago as a waste drainage system in the brain that promotes the elimination of amyloid-beta and tau protein. We here evaluated the relationships between glymphatic system activity and regional brain volumes in PSP patients. Method: Subjects were 24 patients with PSP and 42 healthy participants who underwent diffusion tensor imaging (DTI). We computed the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index as a proxy of glymphatic system activity and estimated the relationships between the DTI-ALPS index and regional brain volume in PSP patients by whole-brain and region-of-interest analyses, including analyses of the midbrain and third and lateral ventricles. Results: The DTI-ALPS index was significantly lower in patients with PSP compared with healthy subjects. Further, there were significant correlations between the DTI-ALPS index and the regional brain volumes in the midbrain tegmentum, pons, right frontal lobe, and lateral ventricles in patients with PSP. Conclusions: Our data suggest that the DTI-ALPS index is a good biomarker for PSP and might be effective to distinguish PSP from other neurocognitive disorders.

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