Cerebrospinal Fluid Cytokines and Neurodegeneration-Associated Proteins in Parkinson's Disease.

Caroline H Williams‐Gray,Sarah F Moore,Roger A Barker,David P Breen,Ruwani S Wijeyekoon,Krista Farrell

doi:10.1002/mds.28015

Abstract

IntroductionImmune markers are altered in Parkinson's disease (PD), but relationships between cerebrospinal fluid (CSF) and plasma cytokines and associations with neurodegeneration‐associated proteins remain unclear.MethodsCSF and plasma samples and demographic/clinical measures were obtained from 35 PD patients. CSF samples were analyzed for cytokines (together with plasma) and for α‐synuclein, amyloid β(1‐42) peptide, total tau, and phospho(Thr231)‐tau.ResultsThere were no CSF–plasma cytokine correlations. Interleukin (IL)‐8 was higher and interferon‐γ, IL‐10, and tumor necrosis factor–α were lower in CSF versus plasma. In CSF, total tau correlated positively with IL‐8 and IL‐1β, whereas α‐synuclein correlated positively with amyloid β(1‐42) and negatively with semantic fluency (a known marker of PD dementia risk).DiscussionCSF and peripheral cytokine profiles in PD are not closely related. Associations between CSF IL‐8 and IL‐1β and tau suggest that CSF inflammatory changes may relate to tau pathology within PD. CSF α‐synuclein/amyloid β may reflect the risk of developing PD dementia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Highlights

Immune markers are altered in Parkinson’s disease (PD), but relationships between cerebrospinal fluid (CSF) and plasma cytokines, and associations with neurodegeneration-associated proteins remain unclear
Associations between CSF IL-8 and IL-1β, and tau suggest CSF inflammatory changes may relate to tau pathology within PD
This study has demonstrated that the cytokine profile in PD CSF does not relate closely to that seen in the periphery, suggesting that factors within the central nervous system (CNS) may play a role in influencing local CNS inflammation

Summary

Introduction

Immune markers are altered in Parkinson’s disease (PD), but relationships between cerebrospinal fluid (CSF) and plasma cytokines, and associations with neurodegeneration-associated proteins remain unclear. CSF samples were analysed for cytokines (together with plasma), and for alpha-synuclein, amyloid beta(1-42) peptide, total tau and phospho(Thr231)-tau. Parkinson’s disease (PD) is associated with central and peripheral immune changes[1]. The cerebrospinal fluid (CSF) is in close contact with the central nervous system (CNS) and studying CSF immune markers and neurodegeneration-associated proteins, alongside paired plasma immune markers may provide additional insights into these relationships in PD. The key neurodegeneration-associated protein involved in PD is alpha-synuclein, with multiple factors leading to abnormal aggregation and pathology. CSF total alpha-synuclein concentration is generally decreased in PD compared to controls[2], possibly reflecting intracellular accumulation/aggregation. PD patients with cognitive impairment and dementia have decreased CSF amyloid beta and increased total tau levels[3]

Objectives

Methods

Results

Conclusion