Inflammation biomarker discovery in Parkinson's disease and atypical parkinsonisms

Abstract

Background: Parkinson’s disease (PD) and atypical parkinsonisms (APD) have overlapping symptoms challenging an early diagnosis. Diagnostic accuracy is important because PD and APD have different prognosis and response to treatment. We aimed to identify diagnostic inflammatory biomarkers of PD and APD in cerebrospinal fluid (CSF) using the multiplex proximity extension assay (PEA) technology and to study possible correlations of biomarkers with disease progression. Methods: CSF from a longitudinal cohort study consisting of PD and APD patients (PD, n = 44; multiple system atrophy (MSA), n = 14; vascular parkinsonism (VaP), n = 9; and PD with VaP, n = 7) and controls (n = 25) were analyzed. Results: Concentrations of CCL28 were elevated in PD compared to controls (p = 0.0001). Five other biomarkers differentiated both MSA and PD from controls (p < 0.05) and 10 biomarkers differentiated MSA from controls, of which two proteins, i.e. beta nerve growth factor (β-NGF) and Delta and Notch like epidermal growth factor-related receptor (DNER), were also present at lower levels in MSA compared to PD (both p = 0.032). Two biomarkers (MCP-1 and MMP-10) positively correlated with PD progression (rho > 0.650; p < 0.01). Conclusions: PEA technique identified potential new CSF biomarkers to help to predict the prognosis of PD. Also, we identified new candidate biomarkers to distinguish MSA from PD.

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

“…Thus, we anticipated that CSF levels of MCP-1 would be increased in PD and/or MSA compared to controls. However, and in agreement with other studies 25 – 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 .…”

“…Also, higher MCP-1 expression has been demonstrated in patients with dementia 32,33 . Thus, MCP-1 levels might be higher in later stages of the disease and be associated with disease progression, as we also observed previously 29 . In the present study, we found a weak positive correlation in the PD group between MCP-1 levels in CSF and both final HY score at 3-year follow-up and progression of this score over a 3-year period.…”

Soluble CD163 Changes Indicate Monocyte Association With Cognitive Deficits in Parkinson's Disease

“…sCD163 is a biomarker widely used to measure an inflammatory component. Accordingly, in PD serum, sCD163 was associated with an increase in the acute‐phase proteins SAA and CRP, which were previously associated with motor impairment and PD dementia 37,49‐51 . Moreover, serum‐sCD163 also correlated with the proinflammatory cytokines TNF‐α and IL‐6, as well as IL‐12/IL‐23p40 and IL‐15, both elevated in PD serum.…”

“…Thus, sCD163 could be partially produced by infiltrating CD163 + monocytes/macrophages and their subsequent local activation. Accordingly, CSF‐sCD163 was correlated with CCL2, CCL4, and CXCL10, chemokines involved in monocyte recruitment and previously correlated with PD symptoms 37‐40 . More importantly, sCD163 was also strongly correlated with regulators of angiogenesis, blood–brain barrier (BBB) extravasation, and/or monocyte brain infiltration or recruitment, 41‐45 which have been reported to be increased in PD, 46‐48 namely, ICAM‐1, VCAM‐1, and VEGF‐D in both serum and CSF, and IL‐8, IL‐15, and PIGF only in CSF.…”

Inflammatory cytokine levels in multiple system atrophy

“…[ 15 – 18 ] At the same time, some studies have used cerebrospinal fluid to detect cytokine levels in patients with MSA, because cerebrospinal fluid specimens are closely related to the brain and are not affected by drugs such as nonsteroidal anti-stimulation drugs. [ 19 – 23 ] Although some studies have evaluated inflammatory cytokines in MSA, the results are not always consistent. [ 15 – 23 ] Hall et al [ 23 ] found IL-8 is increased in patients with MSA compared to healthy controls.…”