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

Gnörich, Johannes; Kusche‐Palenga, Julia; Palleis, Carla; Neubauer, Antonia; Frontzkowski, Lukas; Jäck, Alexander; Kling, Agnes; Bauer, Theresa; Eyob, Hannah; Probst, Katharina; Roemer‐Cassiano, Sebastian N.; Bernhardt, Alexander M.; Katzdobler, Sabrina; Marth, Lena; Zaganjori, Mirlind; Hopfner, Franziska; Zwergal, Andreas; Häckert, Jan; Rullmann, Michael; Sabri, Osama; Barthel, Henryk; Stöcklein, Sophia; Werner, Rudolf A.; Simons, Mikael; Levin, Johannes; Herms, Jochen; Franzmeier, Nicolai; Höglinger, Günter U.; Brendel, Matthias (2026): Longitudinal monitoring of tau aggregation in progressive supranuclear palsy with [ 18 F]PI‐2620 PET. Alzheimer's & Dementia, 22 (2): e71195. ISSN 1552-5260

Abstract

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.

Highlights: Longitudinal tau positron emission tomography (PET) reveals subcortical tau progression in progressive supranuclear palsy over 21 months.
Tau accumulation shows a non-linear trajectory with ceiling effects .
PET signal remains elevated despite neuronal loss due to residual tau pathology.
Functional connectivity predicts similarity in tau accumulation rates across regions.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Nuclear Medicine
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 390857198