Is Neuroinflammation Involved in the Development of Dementia in Patients with Parkinson's Disease?

Song, In‐Uk; Kim, Young-Do; Cho, Hyun-Ji; Chung, Sung Woo

doi:10.2169/internalmedicine.52.0474

Cited by 31 publications

(22 citation statements)

References 30 publications

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“…Epidemiological studies and PD models indicate that aging is the strongest risk factor for PD. Therefore, it has been hypothesized that microglia-mediated neuroinflammation plays an important role in the pathogenesis of PD [4,5]. However, the present study did not show a significant correlation between the serum hs-CRP level, a sensitive marker of systemic inflammation, and aging of patients with PD.…”

Section: Discussioncontrasting

confidence: 90%

“…At the cellular level, significant microglial inflammation is observed in regions of dopaminergic degeneration, and some protection against PD is offered by long-term anti-inflammatory medications [4,5,25]. In addition, microglia-mediated neuroinflammation has been hypothesized to play an important role in the pathogenesis of neurodegenerative diseases such as PD and AD [5,6,26].…”

Section: Discussionmentioning

confidence: 99%

“…This process has gained a great deal of attention in PD, Alzheimer's disease (AD), and other neurodegenerative diseases [2,3]. Microglia-mediated neuroinflammation has been hypothesized to play an important role in the pathogenesis of PD as well as in the cognitive decline observed in patients with AD [4,5,6]. Microglia are involved in immune surveillance in intact brains and become activated in response to inflammation, trauma, ischemia, tumor, and neurodegeneration [7].…”

Section: Introductionmentioning

confidence: 99%

“…This is because hs-CRP increases the paracellular permeability of the blood-brain barrier (BBB) when its concentration exceeds the threshold required to impair the BBB function. The threshold concentration of hs-CRP is easily achieved in states of systemic inflammation, or even in obesity [4,5,6,9,10]. In other words, the interactions of hs-CRP and the BBB are a two-phase process, with increased paracellular permeability at a high dose of hs-CRP that enables its entry into the central nervous system (CNS) and serves to induce reactive gliosis and impair CNS function [9,11,12,13].…”

Section: Introductionmentioning

confidence: 99%

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Serum hs-CRP Levels are Increased in de Novo Parkinson's Disease Independently from Age of Onset

et al. 2014

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Background: Microglia in the brain are the counterpart of macrophages and it functions as a first defense in the brain. The double-edged feature of microglia has explained that the inflammatory state of microglia in aged brains induces them to over-respond to small stimuli that are otherwise well controlled in young brains. The clinical effect of microglia in patients with Parkinson's disease (PD) is poorly defined. This prospective study assessed the peripheral concentrations of hs-CRP, a protein able to reflect neuroinflammation in the CNS, in de novo PD patients with varying ages of onset. Methods: We examined 435 patients with de novo PD and 221 healthy subjects and the differences in hs-CRP between these groups were investigated. The PD group was classified into 4 subgroups according to the age of de novo PD to investigate the relationship between hs-CRP and the aging process in de novo PD. Results: There were significantly higher serum hs-CRP levels in patients with PD compared with healthy subjects. A post-hoc analysis of the 4 PD subgroups showed no significant differences in serum hs-CRP level. Conclusion: We assumed that neuroinflammatory reactions play a role in the pathogenesis of PD, but found no clinical evidence of a neuroprotective effect against PD in young brains. To clarify the role of microglia and aging in the pathogenesis of PD, future longitudinal studies involving a large cohort are required.

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Section: Discussioncontrasting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum hs-CRP Levels are Increased in de Novo Parkinson's Disease Independently from Age of Onset

et al. 2014

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“…Increased peripheral cytokine production influences PD progression [14,15]. In-Uk Song et al [16] reported that the hs-CRP and fibrinogen levels were significantly higher in the PD patients than in the healthy control group. Our results are similar to those of In-Uk Song et al The epidemiological studies of Chen et al reported that chronic use of NSAIDs reduces the risk of development of sporadic PD.…”

Section: Discussionmentioning

confidence: 99%

The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson’s disease

Bulut²,

et al. 2014

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The role of carcinoembryonic antigen (CEA) in Parkinson's disease (PD) has not been previously investigated. The aim of the present study was to evaluate the serum level of carcinoembryonic antigen, high-sensitivity C-reactive protein (hs-CRP), and Neutrophil/lymphocyte ratio (NLR) among patients with Parkinson's disease and to examine the relationship between these inflammatory markers. The cross-sectional design includes 51 patients with Parkinson's disease and 50 age- and sex-matched healthy controls. We investigated the differences in hs-CRP, CEA, and NLR levels between these two groups. CEA was significantly higher in PD patients relative to the control group (mean 2.40 ± 1.51 vs. 1.72 ± 0.87 (ng/mL), respectively; p = 0.015). Mean NLR was significantly higher in PD patients relative to the control group (mean 3.1 ± 1.3 vs. 2.1 ± 0.32, respectively; p < 0.001). Serum level of hs-CRP was higher in PD patients than in control group (mean 1.04 ± 0.62 and 0.54 ± 0.31, respectively; p < 0.01). Correlation analysis revealed significant correlation between hs-CRP, CEA, and Neutrophil/lymphocyte ratio (p < 0.05). This study demonstrates for the first time the association between CEA, hs-CRP, NLR, and PD. We found CEA, hs-CRP, and NLR levels to be significantly higher in the PD patients than in the normal controls.

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Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease

et al. 2016

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IMPORTANCEThe association of nonmotor features and Parkinson disease (PD) is increasingly recognized. Evidence suggests that inflammation may play a role in PD pathologic features and symptoms.OBJECTIVE To quantitatively summarize the peripheral inflammatory cytokine data available for patients with PD.DATA SOURCE A systematic search of peer-reviewed English-language articles from PubMed, PsycINFO, and the Cochrane Library without year limitation was performed from December 7, 2015, to March 23, 2016. The search terms included inflammation or cytokine or chemokine or tumor necrosis factor or interleukin or interferon or C-reactive protein AND Parkinson disease.STUDY SELECTION Studies were included if they provided data on peripheral blood cytokine concentrations in patients with PD and a healthy control group. Studies were excluded if they contained in vitro analysis of stimulated or unstimulated levels of cytokines, samples that overlapped with other studies, patients not diagnosed with PD at blood sampling, or if the cytokine analyzed was assessed in fewer than 3 studies.DATA EXTRACTION AND SYNTHESIS Data were extracted from the 25 included studies encompassing 1547 unique patients with PD and 1107 unique controls by 2 independent investigators. Data were pooled using a random-effects model with the Comprehensive Meta-analysis software. Effect sizes were generated as standardized mean differences of cytokine concentrations between patients with PD and healthy controls and converted to the Hedges g statistic.MAIN OUTCOMES AND MEASURES Blood cytokine concentrations in patients with PD compared with controls. Aberrations in peripheral cytokine levels were hypothesized to be related to PD. RESULTS Among the 2654 study participants, concentrations of interleukin 6 (IL-6) (Hedges g, 0.325; 95% CI, 0.007-0.643; P = .045) in 13 studies, tumor necrosis factor (Hedges g, 0.354; 95% CI, 0.144-0.563; P = .001) in 9 studies, IL-1β (Hedges g, 0.382; 95% CI, 0.142-0.621; P = .002) in 6 studies, C-reactive protein (Hedges g, 0.323; 95% CI, 0.052-0.593; P = .02) in 6 studies, IL-10 (Hedges g, 0.329; 95% CI, 0.051-0.607; P = .02) in 5 studies, RANTES (regulated on activation, normal T-expressed, and presumably secreted) (Hedges g, 0.605; 95% CI, 0.111-1.099; P = .02) in 5 studies, and IL-2 (Hedges g, 0.789; 95% CI, 0.105-1.472; P = .02) in 3 studies were significantly higher in patients with PD compared with healthy controls. No differences were found between patients with PD and healthy controls for concentrations of interferon-γ (Hedges g, 0.745; 95% CI, −0.192 to 1.682; P = .12) in 5 studies, IL-4 (Hedges g, 0.031; 95% CI, −0.191 to 0.253; P = .79) in 3 studies, and IL-8 (Hedges g, 0.072; 95% CI, −0.136 to 0.279; P = .50) in 3 studies. CONCLUSIONS AND RELEVANCEThe findings of the meta-analysis demonstrated higher peripheral concentrations of IL-6, tumor necrosis factor, IL-1β, IL-2, IL-10, C-reactive protein, and RANTES in patients with PD, strengthening the clinical evidence that PD is accompanied by an inflammatory response.

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Is Neuroinflammation Involved in the Development of Dementia in Patients with Parkinson's Disease?

Cited by 31 publications

References 30 publications

Serum hs-CRP Levels are Increased in de Novo Parkinson's Disease Independently from Age of Onset

Serum hs-CRP Levels are Increased in de Novo Parkinson's Disease Independently from Age of Onset

The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson’s disease

Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease

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