Description:
<jats:sec><jats:title>Background</jats:title><jats:p>An involvement of the central-nervous and peripheral, innate and adaptive immune system in the pathogenesis of Parkinson's disease (PD) is nowadays well established.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>We face several open questions in preparation of clinical trials aiming at disease-modification by targeting the immune system: Do peripheral (blood) inflammatory profiles reflect central (CSF) inflammatory processes? Are blood/CSF inflammatory markers associated with CSF levels of neurodegenerative/PD-specific biomarkers?</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using a multiplex assay we assessed 41 inflammatory markers in CSF/serum pairs in 453 sporadic PD patients. We analyzed CSF/serum correlation as well as associations of inflammatory markers with clinical outcome measures (UPDRS-III, H&amp;Y, MoCA) and with CSF levels of α-synuclein, Aβ<jats:sub>1−42</jats:sub>, <jats:italic>t-</jats:italic>Tau, p181-Tau and NFL. All analyses were stratified by sex as the immune system shows relevant sex-specific differences.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Correlations between CSF and serum were sparse and detected in only 25% (9 out of 36) of the analysable inflammatory markers in male PD patients and in only 38% (12 out of 32) of female PD patients. The most important pro-inflammatory mediators associated with motor and cognitive decline as well as with neurodegenerative/PD-specific biomarkers were FABP, ICAM-1, IL-8, MCP-1, MIP-1-beta, and SCF. Results were more robust for CSF than for serum.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Levels of central-nervous and peripheral inflammatory markers might be regulated independently of each other with CSF inflammatory markers reflecting CNS pathology more accurately than peripheral markers. These findings along with sex-specific characteristics have to be considered when designing clinical trials aiming at disease-modification by targeting the immune system.</jats:p></jats:sec>