Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Positron Emission Tomography Study with [ 11 C ] PBR28 and Machine Learning Analysis
Open accessAbstract
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 [ 11 C]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 [ 11 C]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. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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Microglial activation has a specific pattern in MSA.
“suggesting that microglial activation has a specific pattern in MSA, although microglial activation has been considered a common immune response in neurodegenerative diseases.288”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [287]
According to pathological studies and PET imaging of MSA brains, microglial activation and neuroinflammation constitute important features of MSA.
“But according to pathological studies and PET imaging of MSA brains, microglial activation and neuroinflammation constitute important features of MSA.283–287”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [287]
Visual reading of this pattern achieved 100% specificity and 83% sensitivity in discriminating MSA from PD.
“This pattern by visual reading achieved 100% specificity and 83% sensitivity in discriminating MSA from PD,287”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [287]
A [11C] PBR28 PET study observed a conspicuous pattern of increased microglial activation in the cerebellar white matter and lentiform nucleus in MSA compared with PD.
“observed a conspicuous pattern of increased microglial activation in the cerebellar white matter and lentiform nucleus in MSA compared with PD.287”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [287]
PET imaging demonstrated microglial activation in the brains of patients with MSA.
“PET imaging also demonstrated microglial activation in the brains of patients with MSA.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [287]
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Middle Cerebellar Peduncle in Early Stage of Multiple System Atrophy: A THK5351 PET Study
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PET Molecular Probes for Neuroinflammation in Neurodegenerative Diseases: Progress and Prospects
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New Targets for Positron Emission Tomography Imaging in Parkinson´s Disease
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- Authors
- Jucaite, A., Cselényi, Z., Kreisl, W. C., Rabiner, E. A., Varrone, A., Carson, R. E., Rinne, J. O., Savage, A., Schou, M., Johnström, P., Svenningsson, P., Rascol, O., Meissner, W. G., Barone, P., Seppi, K., Kaufmann, H., Wenning, G. K., Poewe, W., & Farde, L.
- Affiliations
- PET Science Centre, Personalized Medicine and Biosamples R&D, AstraZeneca Stockholm Sweden
- Karolinska Institutet (SE)
- Columbia University Irving Medical Center (US)
- King's College London (GB)
- Yale University (US)
- University of Turku (FI)
- AstraZeneca (United States) (US)
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- University of Salerno (IT)
- Innsbruck Medical University (AT)
- New York University (US)
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2021-10-05
- Volume
- 37
- Issue
- 1
- Pages
- 119-129
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W3204534760
- Cited by
- 43
- References
- 50
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 4 · 2023: 8 · 2022: 10
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Movement Disorders (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- AstraZeneca Pharma Poland
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- multiple system atrophy, Parkinson's disease, [11C]PBR28, translocator protein (TSPO), neuroinflammation, differential diagnosis, machine learning, synucleinopathies, lentiform nucleus, cerebellar white matter
- MeSH terms
- Machine Learning, Humans, Neuroglia, Parkinson Disease, Receptors, GABA, Multiple System Atrophy, Positron-Emission Tomography
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