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

INTRODUCTION

Progressive supranuclear palsy (PSP), a 4-repeat tauopathy, can be visualized using [18F]PI-2620 tau positron emission tomography (PET). However, the value of sequential [18F]PI-2620 imaging for tracking tau accumulation during the disease course has not yet been investigated.

METHODS

Twenty-three PSP patients underwent two [18F]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: [18F]PI-2620 PET enables monitoring of tau progression in PSP, indicating network-based tau propagation with saturation in advanced stages.