Cited by 1,200Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsMedical Imaging Techniques and Applications

In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease

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Gerhard, Alexander, Pavese, Nicola, Hotton, Gary, Turkheimer, Federico, Es, Meltem, Hammers, Alexander, Eggert, Karla, Oertel, Wolfgang +2 more·2006·Neurobiology of Disease

Abstract

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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Crossref · 10.1016/j.nbd.2005.08.002

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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.”
  • PET scans of PD patients reveal widespread microglial activation.

    “Additionally, PET scans of PD patients revealed widespread microglial activation.”
  • 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].”

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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
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
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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