@article{dc04516ad43f4a65914b0c5d09b9e5d8,
title = "Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Positron Emission Tomography Study with [11C]PBR28 and Machine Learning Analysis",
abstract = "Background: The clinical diagnosis of multiple system atrophy (MSA) is challenged by overlapping features with Parkinson's disease (PD) and late-onset ataxias. Additional biomarkers are needed to confirm MSA and to advance the understanding of pathophysiology. Positron emission tomography (PET) imaging of the translocator protein (TSPO), expressed by glia cells, has shown elevations in MSA. Objective: In this multicenter PET study, we assess the performance of TSPO imaging as a diagnostic marker for MSA. Methods: We analyzed [11C]PBR28 binding to TSPO using imaging data of 66 patients with MSA and 24 patients with PD. Group comparisons were based on regional analysis of parametric images. The diagnostic readout included visual reading of PET images against clinical diagnosis and machine learning analyses. Sensitivity, specificity, and receiver operating curves were used to discriminate MSA from PD and cerebellar from parkinsonian variant MSA. Results: We observed a conspicuous pattern of elevated regional [11C]PBR28 binding to TSPO in MSA as compared with PD, with “hotspots” in the lentiform nucleus and cerebellar white matter. Visual reading discriminated MSA from PD with 100% specificity and 83% sensitivity. The machine learning approach improved sensitivity to 96%. We identified MSA subtype-specific TSPO binding patterns. Conclusions: We found a pattern of significantly increased regional glial TSPO binding in patients with MSA. Intriguingly, our data are in line with severe neuroinflammation in MSA. Glia imaging may have potential to support clinical MSA diagnosis and patient stratification in clinical trials on novel drug therapies for an α-synucleinopathy that remains strikingly incurable.",
keywords = "microglia, multiple system atrophy, positron emission tomography, translocator protein, [C]PBR28",
author = "Aurelija Jucaite and Zsolt Csel{\'e}nyi and Kreisl, {William C.} and Rabiner, {Eugenii A.} and Andrea Varrone and Carson, {Richard E.} and Rinne, {Juha O.} and Alicia Savage and Magnus Schou and Peter Johnstr{\"o}m and Per Svenningsson and Olivier Rascol and Meissner, {Wassilios G.} and Paolo Barone and Klaus Seppi and Horacio Kaufmann and Wenning, {Gregor K.} and Werner Poewe and Lars Farde",
note = "Funding Information: A.J., Z.C., P.J., M.S., and A.S. were full‐time employees of AstraZeneca. Z.C., P.J., and M.S. have stocks at AstraZeneca. O.R. has served as a scientific advisor for the following companies: AbbVie, Adamas, Acorda, Aguettant, Alkahest, AlzProtect, Apopharma, AstraZeneca, Bial, Biogen, Britannia, Buckwang, Cerevel, Clevexel, Irlab, Eli‐Lilly, Lundbeck, Neuroderm, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Pfizer, Prexton Therapeutics, Sanofi, Servier, Sunovion, Th{\'e}ranexus, Takeda, Teva, UCB, Watermark Research, XenoPort, XO, Zambon; O.R. has received scientific grants from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France‐Parkinson, INSERM‐DHOS Recherche Clinique Translationnelle, The Michael J. Fox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020), ONO Pharma, and Lundbeck. W.G.M. has received fees for editorial activities with Elsevier; has served as an advisor for Lundbeck, Biohaven, and Roche; and has received teaching honoraria from UCB. P.S. reports consultancy for AbbVie and research support from Karin and Sten Mortstedt CBD Solutions AB, Swedish Foundation for Strategic Research, Swedish Research Council, and ALF program from Stockholm City Council. W.P. reports the following disclosures: personal fees from Alterity, AbbVie, Affiris, AstraZeneca, BIAL, Biogen, Britannia, Lilly, Lundbeck, Neuroderm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Roche, Takeda, Teva, UCB, and Zambon (consultancy and lecture fees in relation to clinical drug development programs for PD); royalties from Thieme, Wiley Blackwell, Oxford University Press, and Cambridge University Press; and grant support from The Michael J. Fox Foundation and EU FP7 & Horizon 2020. R.E.C. has received research support from BMS, Cerevel, and Invicro. W.C.K. reports consultancies with Cerveau Technologies, Novartis, and Takeda. A.V. has received research funding from H. Lundbeck A/S and from the Swedish Science Council. L.F. has received research grants from the Swedish Science Council and has stocks at AstraZeneca. K.S. reports personal fees from Teva, UCB, Lundbeck, AOP Orphan Pharmaceuticals AG, Roche, Gr{\"u}nenthal, Stada, Licher Pharma, Biogen, and AbbVie; honoraria from the International Parkinson and Movement Disorders Society; and research grants from FWF Austrian Science Fund, The Michael J. Fox Foundation, and AOP Orphan Pharmaceuticals AG. J.O.R. has received funding for academic studies from the Academy of Finland (grant #310962), the Sigrid Juselius Foundation, and Finnish Governmental Research FUNDING (ERVA) and serves as a consulting neurologist for Clinical Research Services Turku Oy (CRST). H.K. is Editor‐in‐Chief of ; serves as the principal investigator of a clinical trial sponsored by Biogen MA Inc. (TRACK MSA); and has received consultancy fees from Lilly USA LLC, Biohaven Pharmaceuticals Inc., Takeda Pharmaceutical Company Ltd, Ono Pharma UK Ltd, Lundbeck LLC, and Theravance Biopharma US Inc. E.A.R.: InVicro, full time employee. P.B.: advisory board fees from Roche (Swiss), Bial (Portugal), Abbvie (Italy). G.K.W.: no disclosures to report. Clinical Autonomic Research Publisher Copyright: {\textcopyright} 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = oct,
day = "5",
doi = "10.1002/mds.28814",
language = "English",
volume = "37",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "Wiley",
number = "1",
}