Early microglial activation and peripheral inflammation in dementia with Lewy bodies
Open accessAbstract
Inflammation is increasingly recognized as part of the pathology of neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, but its role in dementia with Lewy bodies remains unclear. Using multimodal imaging and peripheral cytokine analysis, we therefore investigated central and peripheral inflammation in this common form of dementia. Nineteen participants with probable dementia with Lewy bodies and 16 similarly aged controls underwent 3 T MRI and PET imaging with 11C-PK11195, a marker of microglial activation in vivo. Peripheral blood inflammatory cytokines were also measured in all subjects, as well as in an additional 10 controls, using the Mesoscale Human Cytokine 36 plex panel and additional assays for high sensitivity c-reactive protein, tumour necrosis factor receptor 1, IL-34, YKL-40 (chitinase-3-like protein 1) and colony stimulating factor 1. To test for the presence of in vivo amyloid, 11C-Pittsburgh compound B PET imaging was also performed in 16 of the dementia with Lewy body participants. Microglial activation was elevated in dementia with Lewy bodies subjects with mild disease when compared to those with moderate/severe impairment, where disease severity was indexed by cognitive performance on the revised Addenbrooke's Cognitive Examination. In patients, strong correlations were found between cognitive performance and 11C-PK11195 non-displaceable binding potential in several regions including the caudate nucleus (R = 0.83, P = 0.00008) and cuneus (R = 0.77, P = 0.0005). Several inflammatory cytokines were altered in the patients compared to controls, with elevated macrophage inflammatory protein-3 (P = 0.001), IL-17A (P = 0.008) and IL-2 (P = 0.046) and reduced IL-8 (P = 0.024). There was no correlation between cortical 11C-Pittsburgh compound B standardized uptake value ratio and clinical features, regional 11C-PK11195 binding or peripheral cytokine levels. Nor was there any regional correlation between 11C-PK11195 non-displaceable binding potentials and 11C-Pittsburgh compound B standardized uptake value ratios. Our findings provide evidence for both central and peripheral inflammatory changes in dementia with Lewy bodies, with microglial activation occurring early in the disease in key regions known to be associated with pathology, before declining as cognition declines. Raised peripheral cytokines associated with T cell function further suggest a role for the adaptive immune system in the pathogenesis of the disease.
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In DLB, microglial activation using PK-PET was shown to occur early in the disease in key regions associated with the pathology.
“In DLB, microglial activation using PK-PET was shown to be occurring early in the disease in key regions associated with the pathology [219].”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [219]
Two studies found increased microglial activation in the early stage of DLB.
“Two studies found increased microglial activation in the early stage of DLB.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [426]
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- Authors
- Surendranathan, A., Su, L., Mak, E., Passamonti, L., Hong, Y. T., Arnold, R., Vázquez Rodríguez, P., Bevan-Jones, W. R., Brain, S. A. E., Fryer, T. D., Aigbirhio, F. I., Rowe, J. B., & O’Brien, J. T.
- Affiliations
- University of Cambridge (GB)
- Southwest University (CN)
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Royal Berkshire NHS Foundation Trust (GB)
- Department of Psychiatry, University of Cambridge, Cambridge, UK
- Corresponding author
- Surendranathan, Ajenthan
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-11-06
- Volume
- 141
- Issue
- 12
- Pages
- 3415-3427
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC6262214
- OpenAlex
- W2900321422
- Cited by
- 154
- References
- 69
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 26 · 2023: 15 · 2022: 30 · 2021: 15 · 2020: 28 · 2019: 9
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- National Institute for Health Research Cambridge Biomedical Research Centre (RG64473)
- Alzheimer’s Research UK
- Bury Free Press
- Wellcome Trust (103838)
- PSP Association
- Alzheimer's Research UK (ARUK-SRF2017B-1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- dementia with Lewy bodies, microglial activation, neuroinflammation, peripheral inflammation, inflammatory cytokines, [11C]PK11195 PET, amyloid imaging, cognitive impairment, disease severity, caudate nucleus, cuneus, IL-17A, interleukin-8, interleukin-2
- MeSH terms
- Aged, Brain, Encephalitis, Female, Humans, Inflammation, Magnetic Resonance Imaging, Male, Cytokines, Microglia, Disease Progression, Lewy Body Disease, Positron-Emission Tomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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