Cerebrospinal fluid concentrations of inflammatory markers in Parkinson\u2019s disease and atypical parkinsonian disorders

Sara Hall,Shorena Janelidze,Oskar Hansson,Henrik Zetterberg,Yulia Surova,Håkan Widner

doi:10.1038/s41598-018-31517-z

Abstract

Inflammation has been implicated in the pathogenesis of Parkinson’s disease (PD). We here investigate levels of inflammatory biomarkers in cerebrospinal fluid (CSF) in PD and atypical parkinsonian disorders (APD) compared with neurologically healthy controls. We included 131 patients with PD and 27 PD with dementia (PDD), 24 with multiple system atrophy (MSA), 14 with progressive supranuclear palsy (PSP) and 50 controls, all part of the Swedish BioFINDER study. CSF was analyzed for CRP, SAA, IL-6, IL-8, YKL-40 and MCP-1 (CCL2) as well as α-synuclein (α-syn), tau, tau phosphorylated at Thr181 (P-tau), Aβ42 and NfL. In this exploratory study, we found higher levels of the inflammatory biomarker SAA in PDD and MSA compared with controls and PD and higher levels of CRP in PDD and MSA compared with PD. YKL-40 was lower in PD compared with controls. There were multiple positive correlations between the inflammatory markers, α-syn and markers of neuroaxonal injury (NfL and tau). In PD, higher levels of inflammatory biomarkers correlated with worse motor function and cognitive impairment. Thus, inflammatory biomarkers were increased in PDD and MSA. Furthermore, inflammatory biomarkers correlated with more severe disease regarding motor symptoms and cognitive impairment in PD, indicating an association between inflammation and more aggressive disease course. However, the results need confirmation in follow-up studies.

Highlights

During the last couple of decades, inflammation has gained support in the pathogenesis of Parkinson’s disease (PD)[1]
No significant correlations were found between, progressive supranuclear palsy (PSP) Rating Scale (PSPRS) motor score or total score and inflammatory markers. In this cross-sectional study, we show that the inflammatory markers CRP and SAA are higher in PD with dementia (PDD) and multiple system atrophy (MSA) compared with PD and in the case of SAA compared with controls
Microglia activation in PDD has been shown to correlate with decreased glucose metabolism and worse results on MMSE43,44

Summary

Introduction

During the last couple of decades, inflammation has gained support in the pathogenesis of Parkinson’s disease (PD)[1]. Increased expression of inflammatory mediators including cytokines and chemokines have been found in post mortem studies in PD4. Microglia are resident immunocompetent and phagocytic cells in the central nervous system (CNS) They can be beneficial and serve as scavengers, phagocytosing dead cells and releasing neurotrophic substances, but they can be harmful, upregulating a variety of proinflammatory and neurotoxic substances such as reactive oxygen species and cytokines[5]. Astrocytes are immunocompetent cells that are sensitive to proinflammatory cytokines and chemokines They are thought to be activated as a response to injury-induced cytokine release[12], and GFAP-positive astrocytes have been found to correlate inversely with dopaminergic cell death in PD13. A recent study found increased levels of YKL-40 in both CSF and brain tissue in patients with Alzheimer’s disease and Creutzfeldt-Jacob but unchanged in the PDD/DLB group compared with controls with neurological controls[17]. Our group has previously shown increased levels of IL-8 in PDD compared with controls[23]

Methods

Results

Conclusion