Longitudinal monitoring of tau aggregation in progressive supranuclear palsy with [ 18 F]PI‐2620 PET

Abstract INTRODUCTION Progressive supranuclear palsy (PSP), a 4‐repeat tauopathy, can be visualized using [ 18 F]PI‐2620 tau positron emission tomography (PET). However, the value of sequential [ 18 F]PI‐2620 imaging for tracking tau accumulation during the disease course has not yet been investigated. METHODS Twenty‐three PSP patients underwent two [ 18 F]PI‐2620 PET scans (interval: 21.4 ± 4.3 months) and were compared to cross‐sectional data from 25 healthy controls. Regional volume of distribution ratio values were analyzed for longitudinal tau changes, clinical correlations, and network‐based propagation. Post mortem analyses examined neuronal density and AT8 tau pathology. RESULTS Subcortical tau PET signals increased, strongest in the globus pallidus internus ( P < 0.0001). Patients with low baseline tau showed the largest increases. Despite clinical worsening (Progressive Supranuclear Palsy Rating Scale +48%), tau PET change did not correlate with symptom progression. Tau accumulation followed functional connectivity ( R = 0.34, P < 0.0001). Post mortem data linked elevated tau PET to higher AT8 burden despite neuronal loss. DISCUSSION [ 18 F]PI‐2620 PET enables monitoring of tau progression in PSP, indicating network‐based tau propagation with saturation in advanced stages.