Immune Cell Activation in the Cerebrospinal Fluid of Patients With Parkinson's Disease

Schröder, Jens Burchard; Pawlowski, Matthias; Hörste, Gerd Meyer zu; Groß, Catharina C.; Wiendl, Heinz; Meuth, Sven G.; Ruck, Tobias; Warnecke, Tobias

doi:10.3389/fneur.2018.01081

Cited by 110 publications

(88 citation statements)

References 45 publications

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“…However, a neuroprotective role and support in repair functions have also been attributed to IL9 [51,52]. Accordingly, our finding of lower IL9 serum concentrations in PD individuals might suggest that dysregulated IL9 signaling could contribute to impaired neuroprotection/repair capacity in PD [53].…”

Section: Discussionmentioning

confidence: 71%

Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study

Picca

Guerra

Calvani

et al. 2020

JCM

104

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Systemic inflammation and mitochondrial dysfunction are involved in neurodegeneration in Parkinson’s disease (PD). Extracellular vesicle (EV) trafficking may link inflammation and mitochondrial dysfunction. In the present study, circulating small EVs (sEVs) from 16 older adults with PD and 12 non-PD controls were purified and characterized. A panel of serum inflammatory biomolecules was measured by multiplex immunoassay. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers (adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2)) were quantified in purified sEVs by immunoblotting. Relative to controls, PD participants showed a greater amount of circulating sEVs. Levels of CD9 and CD63 were lower in the sEV fraction of PD participants, whereas those of CD81 were similar between groups. Lower levels of ATP5A, NDUFS3, and SDHB were detected in sEVs from PD participants. No signal was retrieved for UQCRC2, MTCOI, or NDUFB8 in either participant group. To identify a molecular signature in circulating sEVs in relationship to systemic inflammation, a low level-fused (multi-platform) partial least squares discriminant analysis was applied. The model correctly classified 94.2% ± 6.1% PD participants and 66.7% ± 5.4% controls, and identified seven biomolecules as relevant (CD9, NDUFS3, C-reactive protein, fibroblast growth factor 21, interleukin 9, macrophage inflammatory protein 1β, and tumor necrosis factor alpha). In conclusion, a mitochondrial signature was identified in circulating sEVs from older adults with PD, in association with a specific inflammatory profile. In-depth characterization of sEV trafficking may allow identifying new biomarkers for PD and possible targets for personalized interventions.

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Section: Discussionmentioning

confidence: 71%

Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study

Picca

Guerra

Calvani

et al. 2020

JCM

104

View full text Add to dashboard Cite

show abstract

“…However, and in agreement with other studies [25][26][27][28][29] , we found that CSF levels of MCP-1 are comparable in PD, MSA and controls. In contrast, other studies described increased levels of MCP-1 in CSF of either PD or MSA patients compared to controls 30,31 . An explanation for these discrepancies might be differences in clinical features and pathological state across the various cohorts of patients.…”

Section: Discussionmentioning

confidence: 73%

Cerebrospinal fluid monocyte chemoattractant protein 1 correlates with progression of Parkinson’s disease

Santaella

Kuiperij

Rumund

et al. 2020

npj Parkinsons Dis.

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Parkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging a correct early diagnosis. Prognostic information is needed to predict disease progression and provide appropriate counseling. Neuroinflammation plays a role in the pathology of both disorders, as shown in genetic and postmortem tissue studies. Monocyte chemoattractant protein 1 (MCP-1) and neuroleukin (NLK) are two inflammatory proteins with potential to serve as biomarkers of the neuroinflammatory process. Here, we aimed to study the biomarker potential of both MCP-1 and NLK protein levels in cerebrospinal fluid (CSF) from a longitudinal cohort study (Radboudumc, Nijmegen, The Netherlands), consisting of PD patients (n = 46), MSA patients (n = 17) and control subjects (n = 52) using ELISA. We also correlated MCP-1 and NLK levels in CSF to several parameters of disease. We showed that MCP-1 levels in CSF positively correlate with PD progression (ρ = 0.363; p = 0.017) but could not differentiate between PD, MSA, and controls. NLK levels in CSF neither differentiated between PD, MSA, and controls, nor correlated with disease progression. Our results indicate that MCP-1 levels in CSF cannot distinguish between PD, MSA, and controls but correlate with disease progression in PD patients, suggesting that neuroinflammation is associated with clinical progression in PD. The correlation with disease progression was only moderate, so MCP-1 levels in CSF should be included in a larger battery of prognostic biomarkers that also tackle different pathophysiological processes.

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“…This neuroprotective role of IL-10 has been extensively studied in PD, an example of which is a study showing that administration of a recombinant human IL-10 in the PD model improves forelimb akinesia [45]. However, definitive IL-10 levels in PD are equivocal [46][47][48]. Larsson et al demonstrated that IL-10 mRNA expression was higher in the GG, rather than the AA genotype [49], suggesting that A allele carriers with the IL-10 -1082 G/A genotype, may express low IL-10 levels.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-related gene polymorphisms associated with Parkinson’s disease: an updated meta-analysis

Ulhaq

Garcia

2020

Egypt J Med Hum Genet

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Background: Strong evidence supports the involvement of inflammation processes in the development and progression of Parkinson's disease (PD), where increasingly correlations have been identified between genetic variations in inflammation-related genes and PD. However, data varies between studies. Therefore, we conducted a meta-analysis to clarify associations between inflammation-related gene polymorphisms and PD risk. Methods: All studies were identified through online databases. Pooled and stratified groups based on racial descent were assembled to evaluate associations between polymorphisms and PD. Results: The pooled results showed that protective effects for PD were observed for (1)

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Immune Cell Activation in the Cerebrospinal Fluid of Patients With Parkinson's Disease

Cited by 110 publications

References 45 publications

Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study

Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study

Cerebrospinal fluid monocyte chemoattractant protein 1 correlates with progression of Parkinson’s disease

Inflammation-related gene polymorphisms associated with Parkinson’s disease: an updated meta-analysis

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