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Cited by 254Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients

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Doorn, Karlijn J, Moors, Tim, Drukarch, Benjamin, van de Berg, Wilma DJ, Lucassen, Paul J, van Dam, Anne-Marie·2014·Acta Neuropathologica Communications
DOI 10.1186/s40478-014-0090-1PMC PMC4224021
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Abstract

Next to α-synuclein deposition, microglial activation is a prominent pathological feature in the substantia nigra (SN) of Parkinson's disease (PD) patients. Little is known, however, about the different phenotypes of microglia and how they change during disease progression, in the SN or in another brain region, like the hippocampus (HC), which is implicated in dementia and depression, important non-motor symptoms in PD. We studied phenotypes and activation of microglia in the SN and HC of established PD patients (Braak PD stage 4–6), matched controls (Braak PD stage 0) and of incidental Lewy Body disease (iLBD) cases (Braak PD stage 1–3) that are considered a prodromal state of PD. As recent experimental studies suggested that toll-like receptor 2 (TLR2) mediates α-synuclein triggered microglial activation, we also studied whether TLR2 expression is indeed related to pathology in iLBD and PD patients. A clear α-synuclein pathology-related increase in amoeboid microglia was present in the HC and SN in PD. Also, morphologically primed/reactive microglial cells, and a profound increase in microglial TLR2 expression were apparent in iLBD, but not PD, cases, indicative of an early activational response to PD pathology. Moreover, TLR2 was differentially expressed between the SN and HC, consistent with a region-specific pattern of microglial activation. In conclusion, the regional changes in microglial phenotype and TLR2 expression in primed/reactive microglia in the SN and HC of iLBD cases indicate that TLR2 may play a prominent role in the microglial-mediated responses that could be important for PD progression.

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  • In Parkinson's disease, an increased number of amoeboid, CD68-positive microglia were found compared to incidental Lewy body disease and control cases.

    “In Parkinson’s disease, an increased number of amoeboid, CD68-positive microglia were found compared to incidental Lewy body disease and control cases [103], suggesting active phagocytosis.”

    From Beyond Activation: Characterizing Microglial Functional Phenotypes (2021) · cites this paper as [103]

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References 67 · Cited by 254

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Authors
Doorn, K. J., Moors, T., Drukarch, B., van de Berg, W. D., Lucassen, P. J., & van Dam, A.-M.
Affiliations
  • Amsterdam Neuroscience (NL)
  • University of Amsterdam (NL)
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2014-08-07
Volume
2
Issue
1
Pages
90-90
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-014-0090-1
PMC
PMC4224021
OpenAlex
W2127726976
Cited by
254
References
67
Citations by year
2026: 7 · 2025: 12 · 2024: 23 · 2023: 27 · 2022: 34 · 2021: 37 · 2020: 36 · 2019: 26 · 2018: 16 · 2017: 12 · 2016: 13 · 2015: 8 · 2014: 3
FWCI
6.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Internationale Stichting Alzheimer Onderzoek
  • Alzheimer Nederland
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
microglial activation, microglial phenotype, TLR2, Parkinson's disease, incidental Lewy body disease, substantia nigra, hippocampus, alpha-synuclein, amoeboid microglia, prodromal Parkinson's disease, non-motor symptoms
MeSH terms
CD68 Molecule, Aged, Aged, 80 and over, Brain, Female, Hippocampus, Humans, Male, Middle Aged, Neurons, Parkinson Disease, Phenotype, Substantia Nigra, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Microglia, Lewy Body Disease, Toll-Like Receptor 2, alpha-Synuclein

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