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Neuroinflammation and protein pathology in Parkinson's disease dementia
Kouli A, Camacho M, Allinson K, Williams-Gray CH.. Acta neuropathologica communications, 2020-12-03
Topic: Brain proteins, microglia and lab models
Parkinson's disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer's disease-type pathology. Whilst immune activation is well-described in Parkinson's disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4 + T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4 + T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Kouli, A., Camacho, M., Allinson, K., & Williams-Gray, C. H. (2020). Neuroinflammation and protein pathology in Parkinson's disease dementia. Acta neuropathologica communications. https://doi.org/10.1186/s40478-020-01083-5
Vancouver
Kouli A, Camacho M, Allinson K, Williams-Gray CH. Neuroinflammation and protein pathology in Parkinson's disease dementia. Acta neuropathologica communications. 2020. doi:10.1186/s40478-020-01083-5. PMID: 33272323.
BibTeX
@article{kouli2020-33272323,
author = {Kouli, A. and Camacho, M. and Allinson, K. and Williams-Gray, C. H.},
title = {{Neuroinflammation and protein pathology in Parkinson's disease dementia}},
journal = {Acta neuropathologica communications},
year = {2020},
doi = {10.1186/s40478-020-01083-5},
pmid = {33272323},
url = {https://doi.org/10.1186/s40478-020-01083-5}
}
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Key findings
- Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases.
- Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region.
- Significant infiltration of CD4 + T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala.
- Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala.
Why it matters
This post-mortem study found increased α-synuclein pathology and activated microglia in Parkinson's disease dementia compared with Parkinson's disease without dementia. It is about neuroinflammation and protein pathology in Parkinson's disease dementia, not about treating or curing Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 190 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.8 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 8.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 104 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Caroline H. Williams‐Gray: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33272323) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-020-01083-5
- PubMed: 33272323
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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