In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
Open accessAbstract
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia. We examined 18 PD patients clinically and with [11C](R)-PK11195 and [18F]-dopa PET. Compared to 11 normal controls, the PD patients showed significantly increased mean levels of [11C](R)-PK11195 binding in the pons, basal ganglia and frontal and temporal cortical regions. Eight PD patients were examined longitudinally, and their [11C](R)-PK11195 signal remained stable over 2 years. Levels of microglial activation did not correlate with clinical severity or putamen [18F]-dopa uptake. Our in vivo findings confirm that widespread microglial activation is associated with the pathological process in PD. The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.
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PET studies show widespread proinflammatory microglia in PD, but this response does not correlate with clinical severity, suggesting it occurs early.
“Positron-emission tomography (PET) studies show widespread proinflammatory microglia, but this response does not correlate with clinical severity, suggesting it occurs early in the disease61.”
From Microglia in neurodegeneration (2018) · cites this paper as [61]
Microglial activation is discovered not only in individuals with long-term illnesses but also in patients who were just diagnosed with PD.
“Notably, microglial activation was discovered not only in individuals with long-term illnesses but also in patients who were just diagnosed.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [214]
PET scans of PD patients reveal widespread microglial activation.
“Additionally, PET scans of PD patients revealed widespread microglial activation.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [214]
In humans, Parkinson's disease is associated with neuroinflammation in both postmortem and in vivo analyses.
“In humans, PD is associated with neuroinflammation in both postmortem [171] and in vivo analysis [172, 173].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [173]
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- Authors
- Gerhard, A., Pavese, N., Hotton, G., Turkheimer, F., Es, M., Hammers, A., Eggert, K., Oertel, W., Banati, R. B., & Brooks, D. J.
- Affiliations
- Imperial College London (GB)
- UCL Queen Square Institute of Neurology (GB)
- Philipps University of Marburg (DE)
- The University of Sydney (AU)
- Corresponding author
- Gerhard, Alexander
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 21
- Issue
- 2
- Pages
- 404-412
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2101243397
- Cited by
- 1,200
- References
- 45
- Citations by year
- 2026: 41 · 2025: 65 · 2024: 83 · 2023: 55 · 2022: 95 · 2021: 85 · 2020: 107 · 2019: 70 · 2018: 70 · 2017: 73 · 2016: 62 · 2015: 52 · 2014: 53 · 2013: 55 · 2012: 56
- FWCI
- 12.52
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Parkinson's disease, microglial activation, [11C](R)-PK11195, translocator protein (TSPO), positron emission tomography, 18F-DOPA PET, basal ganglia, passive optical networks, cortical microglia, longitudinal stability, cytokine production, Lewy bodies
- MeSH terms
- Aged, Benzodiazepines, Brain, Carbon Radioisotopes, Diagnostic Imaging, Female, Humans, Isoquinolines, Male, Middle Aged, Parkinson Disease, Microglia, Positron-Emission Tomography
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