Striatal Tau Pathology Underlies Monoaminergic Disruption in Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is a tauopathy marked by widespread tau aggregation and prominent monoaminergic dysfunction, yet the relationship between regional tau burden and monoaminergic impairment remains unclear. In this study, we determine whether regional tau burden is associated with nigrostriatal monoaminergic dysfunction in PSP using PET imaging.

A subset of 20 patients with PSP and monoaminergic impairment, identified by 18 F-FP-DTBZ PET, was recruited and subsequently underwent 18 F-APN-1607 PET to assess tau deposition. All images were spatially normalized and analyzed based on predefined volumes of interest. Erosion-based cerebral white matter was used as the reference region to calculate standardized uptake value ratios (SUVRs) for 18 F-APN-1607 PET.

The SUVRs of 18 F-APN-1607 PET differed significantly between patients with PSP and healthy controls in the globus pallidus, substantia nigra, subthalamus nucleus, and red nucleus, while a significant difference in 18 F-FP-DTBZ SUVRs was observed in all the striatal regions and substantia nigra. Regression analysis discovered negative associations between tau load and monoaminergic disruption in the putamen and caudate, whereas tau accumulation in the substantia nigra was not significantly associated with nigrostriatal impairment.

The pallido-nigro-luysian axis and nigrostriatal system serve as sensitive targets for detecting tau deposition and monoaminergic disruption in PSP. Local striatal tau pathology and tau burden were associated with monoaminergic disruption in PSP.