Inflammation biomarker discovery in Parkinson’s disease and atypical parkinsonisms

Santaella, Anna; Kuiperij, H. Bea; Rumund, Anouke van; Esselink, Rianne A.J.; Gool, Alain J. van; Bloem, Bastiaan R.; Verbeek, Marcel M.

doi:10.1186/s12883-020-1608-8

Cited by 60 publications

(46 citation statements)

References 45 publications

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“…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, 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.…”

Section: Discussionmentioning

confidence: 64%

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

Nissen

Ferreira

Schulte

et al. 2020

Preprint

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Parkinson's disease is a neurodegenerative disorder with a significant immune component. Numerous studies have reported alterations on immune biomarkers in CSF and serum that associate with symptoms in PD patients. However, it is unclear, which specific immune cells are responsible for the changes in those biomarkers; since most of these cytokines or chemokines, can be produced by a variety of immune cells, or even neurons or glia cells in the brain. Here, we investigate a monocyte/macrophage-specific biomarker: sCD163, the soluble form of the receptor CD163. Our data from tow cohorts show that the CSF-sCD163 increases as the disease progresses, together with a correlated increase in PD-specific as well as neurodegeneration-associated disease biomarkers: alpha-synuclein, tau, and phosphorylated-Tau. Moreover, CSF-sCD163 levels were inversely correlated to the cognitive scores MMSE and MOCA, with higher sCD163 indicating lower cognitive capacity. sCD163 was also increased in serum, although only in female PD patients, suggesting a gender distinctive monocyte-related immune response. CSF-sCD163 also correlated with molecules associated with endothelial cells, tissue infiltration, and activation of B cells and T cells in the PD patients. This suggests activation of both the adaptive and the innate immune system along with recruitment of lymphocytes and monocytes to sites of inflammation in the brain. In serum, sCD163 was associated with pro-inflammatory cytokines and acute phase proteins, suggesting a relation to chronic systemic inflammation. Interestingly, our in vitro study suggests that sCD163 might enhance alpha-synuclein uptake by myeloid cells without direct binding, thus participating in the clearance of alpha-synuclein. Accordingly, our data supports sCD163 as a potential cognition-related biomarker in PD and corroborates a role for monocytes both in peripheral and brain immune responses that could have direct consequences in the handling of alpha-synuclein

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Section: Discussionmentioning

confidence: 64%

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

Nissen

Ferreira

Schulte

et al. 2020

Preprint

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“…IL-6 is an important cytokine in the CNS, and several neurological pathologies are associated with increased expression of this cytokine in brain [37]. MCP-1 has been described as a biomarker positively correlated with PD progression [38]. In addition, LAB mixture administration to MPTP injected mice increased significantly the IL-10 concentration in brains compared to Control animals.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects associated with immune modulation by selected lactic acid bacteria in a Parkinson's disease model

et al. 2020

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“…Corroborating the inflammation in PD and its detrimental role, increase in the C-reactive protein (CRP), an acute phase protein, can predict cognitive decline [ 125 ] PD prognosis [ 154 ] and correlated to severe motor symptoms in PD patients [ 151 ]. Moreover, the “pro-inflammatory profile” found in the serum of newly diagnosed PD patients (Table 2 ) was associated with lower motor scores and faster motor decline [ 187 ].…”

Section: Introductionmentioning

confidence: 99%

Periphery and brain, innate and adaptive immunity in Parkinson’s disease

2021

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Parkinson’s disease (PD) is a neurodegenerative disorder where alpha-synuclein plays a central role in the death and dysfunction of neurons, both, in central, as well as in the peripheral nervous system. Besides the neuronal events observed in patients, PD also includes a significant immune component. It is suggested that the PD-associated immune response will have consequences on neuronal health, thus opening immunomodulation as a potential therapeutic strategy in PD. The immune changes during the disease occur in the brain, involving microglia, but also in the periphery with changes in cells of the innate immune system, particularly monocytes, as well as those of adaptive immunity, such as T-cells. This realization arises from multiple patient studies, but also from data in animal models of the disease, providing strong evidence for innate and adaptive immune system crosstalk in the central nervous system and periphery in PD. Here we review the data showing that alpha-synuclein plays a crucial role in the activation of the innate and adaptive immune system. We will also describe the studies suggesting that inflammation in PD includes early changes in innate and adaptive immune cells that develop dynamically through time during disease, contributing to neuronal degeneration and symptomatology in patients. This novel finding has contributed to the definition of PD as a multisystem disease that should be approached in a more integratory manner rather than a brain-focused classical approach.

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Inflammation biomarker discovery in Parkinson’s disease and atypical parkinsonisms

Cited by 60 publications

References 45 publications

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”

Neuroprotective effects associated with immune modulation by selected lactic acid bacteria in a Parkinson's disease model

Periphery and brain, innate and adaptive immunity in Parkinson’s disease

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