Objective: To investigate the relationship between cerebrospinal fluid (CSF) proteins and cytokines, and their correlation with clinical measures in PD.

Background: Several studies have investigated associations between CSF neurodegeneration-related proteins (alpha-synuclein, tau, amyloid-beta) or CSF cytokines and Parkinson’s disease (PD). However their findings have been inconsistent and few studies have explored whether these CSF markers are inter-related.

Methods: Patients were recruited from the PD research clinic at the Brain Repair Centre, Cambridge and underwent lumbar puncture. Demographic data was collected along with their UPDRS and neuropsychological profile. 2-5ml of CSF was collected, centrifuged and stored at -80°C prior to analysis using Mesoscale Discovery platform electrochemiluminescence assays (Proinflammatory panel-1(IL1β, IL2, IL4, IL6, IL8, IL10, IL12p70, IL13, TNFα, IFNy), alpha-synuclein, amyloid beta, tau and phospho(Thr231)-tau). Statistical analysis was performed using IBM SPSS version 21, with log10 transformation of variables prior to analysis.

Results: 35 CSF samples were obtained. The only significant clinical correlate was between higher CSF alpha-synuclein levels and poorer semantic fluency (Pearson’s r= -0.530,p=0.003), which remained significant on multivariate linear regression after adjustment for potential confounders(B=-0.435, p=0.016). In terms of CSF proteins and cytokines, tau correlated with IL1B (r=0.554, p=0.002) and IL8 (r=0.591,p<0.001) and phospho-tau correlated negatively with IL1B (r=-0.537,p=0.022), IL2 (r=-0.667, p=0.001) and TNF α (r=-0.456,p=0.043). Amyloid beta levels correlated negatively with IL4 (r=-0.731, p=0.025). Multivariate linear regression analyses confirmed significant associations between tau, and IL8 (B=0.552,p=0.001) and IL1β (B=0.335,p=0.025) independently of the effects of relevant covariates.

Conclusions: This study provides preliminary evidence of an association between CSF tau and some inflammatory cytokines, suggesting that CSF immune changes may be related to the neurodegenerative pathology of PD. The negative correlation between CSF alpha-synuclein and semantic fluency adds to existing literature suggesting that CSF alpha-synuclein may be a potential biomarker for cognitive impairment in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/associations-between-cerebrospinal-fluid-proteins-and-cytokines-in-parkinsons-disease/