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Published on: March 1, 2011
Cerebrospinal fluid pro-inflammatory cytokines differentiate parkinsonian syndromes
C Starhof1, K Winge2,3, N H H Heegaard4,5
1Department of Neurology, Bispebjerg University Hospital, Bispebjerg Bakke 23, Copenhagen, Denmark. CSTA0017@regionh.dk.
Introduction:
Neuroinflammation has been established to be part of the neuropathological changes in Parkinson's disease (PD) and atypical parkinsonism (APD). Activated microglia play a key role in neuroinflammation by release of cytokines. Evidence of the disparity, if any, in the neuroinflammatory response between PD and APD is sparse. In this study, we investigated CSF cytokine profiles in patients with PD, multiple system atrophy (MSA), or progressive supranuclear palsy (PSP).
Methods:
On a sensitive electrochemiluminescence-based platform (Quickplex, Meso Scale Discovery®), we examined a panel of C-reactive protein (CRP) and eight selected cytokines, IFN-γ, IL-10, IL-18, IL-1β, IL-4, IL-6, TGF-β1, and TNF-α, among patients with PD (n = 46), MSA (n = 35), and PSP (n = 39) or controls (n = 31). Additionally, CSF total tau protein levels were measured as a marker of nonspecific neurodegeneration for correlation estimates.
Results:
CRP and the pro-inflammatory cytokines TNF-α, IL-1β, and Il-6 were statistically significantly elevated in MSA and PSP patients compared to PD patients but not compared to control patients. No analytes differed statistically significantly between MSA and PSP patients. The best diagnostic discrimination, evaluated by ROC curve (AUC 0.77, p = 007, 95% CI 0.660-0.867), between PD and MSA patients was seen for a subset of analytes: CRP, TNF-α, IL-1β, and IFN-γ.
Conclusion:
Among the investigated cytokines and CRP, we found a statistically significant increase of microglia-derived cytokines in MSA and PSP patients compared to PD patients.
Insights
Neuroinflammation markers are elevated in atypical parkinsonism (MSA, PSP) compared to Parkinson
Area of Science:
- Neuroscience
- Immunology
- Neurology
Background:
- Neuroinflammation, characterized by activated microglia and cytokine release, is implicated in Parkinson's disease (PD) and atypical parkinsonism (APD).
- Limited research exists on the specific differences in neuroinflammatory responses between PD and APD.
- This study focuses on comparing cerebrospinal fluid (CSF) cytokine profiles in PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).
Purpose of the Study:
- To investigate and compare CSF cytokine profiles in patients with PD, MSA, and PSP.
- To identify potential differences in neuroinflammation between PD and APD.
- To explore the diagnostic utility of specific cytokines and C-reactive protein (CRP) in differentiating these conditions.
Main Methods:
- Analyzed CSF samples from patients with PD (n=46), MSA (n=35), PSP (n=39), and controls (n=31).
- Measured C-reactive protein (CRP) and eight cytokines (IFN-γ, IL-10, IL-18, IL-1β, IL-4, IL-6, TGF-β1, TNF-α) using electrochemiluminescence.
- Assessed CSF total tau protein levels to correlate with neurodegeneration.
Main Results:
- Elevated levels of CRP and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) were observed in MSA and PSP patients compared to PD patients.
- No significant differences in these analytes were found between MSA and PSP patients.
- A combination of CRP, TNF-α, IL-1β, and IFN-γ showed diagnostic potential (AUC 0.77) for distinguishing PD from MSA.
Conclusions:
- Patients with MSA and PSP exhibit significantly higher levels of microglia-derived cytokines and CRP compared to PD patients.
- These findings suggest distinct neuroinflammatory profiles in different parkinsonian syndromes.
- Specific cytokine patterns may aid in differentiating PD from APD, particularly MSA.
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