Eidson LN et al. – In this study, the authors measured inflammatory proteins in serum and cerebrospinal fluid (CSF) of a small group of patients with Parkinson’s disease (PD) to define inflammatory signatures that help in elucidating the underlying mechanisms of disease pathogenesis. A panel of reliably measurable inflammatory factors was identified in serum and CSF, which can help in distinguishing patients with PD versus healthy controls (HC) and monitoring inflammation with disease progression or in response to interventional therapies. This panel can facilitate generation of hypotheses and feasible experimental designs and help in identifying biomarkers of neurodegenerative disease by focusing on samples, which remain stable irrespective of the time of sample collection.

Methods

• Inflammatory proteins in serum and CSF of a small cohort of PD (n = 12) and age–matched HC subjects (n = 6) were measured at 11 time points across 24 hours to identify potential diurnal variation; demonstrate differences between PD and HC; correlate CSF levels of amyloid beta (Aβ) and alpha–synuclein; and generate data–driven hypotheses, pertaining to candidate biomarkers of PD.

Results

• Although the other factors showed significant variability by time and disease state for each sample, serum interferon gamma (IFNγ), tumor necrosis factor (TNF), and neutrophil gelatinase–associated lipocalin were stable across 24 hours and different between PD and HC.
• C–reactive protein was the only factor that demonstrated a strong linear relationship between CSF and serum.
• Significantly different relationships were reported between CSF Aβ proteins and α–synuclein, and specific inflammatory factors in PD and HC subjects.
• A positive correlation was observed between CSF, IFNγ, and serum interleukin (IL)–8 with clinical measures of PD.
• PD and HC were discriminated with a minimum of 82% sensitivity and 83% specificity using serum TNF and CSF α–synuclein.