Year: 2020
Type: article
Study design: Observational Study
Abstract: Importance: Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. Objective: To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants: In this cross-sectional study, participants underwent dynamic 18F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. Main Outcomes and Measures: Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, 18F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. Results: Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable 18F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with 18F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP-non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. Conclusions and Relevance: This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.
Source: JAMA Neurology
Authors: Matthias Brendel, Henryk Barthel, Thilo van Eimeren, Ken Marek, Leonie Beyer, Mengmeng Song, Carla Palleis, Mona Gehmeyr, Urban Fietzek, Gesine Respondek, Julia Sauerbeck, Alexander Nitschmann, Christian Zach, Jochen Hammes, Michael T. Barbe, Oezguer Onur, Frank Jessen, Dorothee Saur, Matthias L. Schroeter, Jost-Julian Rumpf, Michael Rullmann, Andreas Schildan, Marianne Patt, Bernd Neumaier, Olivier Barret, Jennifer Madonia, David S. Russell, Andrew Stephens, Sigrun Roeber, Jochen Herms, Kai Bötzel, Joseph Classen, Peter Bartenstein, Victor Villemagne, Johannes Levin, Günter U. Höglinger, Alexander Drzezga, John Seibyl, Osama Sabri
Institutions: LMU Klinikum, Ludwig-Maximilians-Universität München, Leipzig University, German Center for Neurodegenerative Diseases, University Hospital Cologne, Invicro (United States), Medizinische Hochschule Hannover, Max Planck Institute for Human Cognitive and Brain Sciences, Forschungszentrum Jülich, Institut für Neuropathologie, Munich Cluster for Systems Neurology, The University of Melbourne, Austin Hospital, Austin Health, Technical University of Munich
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W3038832112