Blood Markers of Inflammation, Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease

ABSTRACT Background Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression. Objective The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high‐throughput sandwich immune multiplex panels in deeply phenotyped PD. Methods Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug‐naive at baseline (BL) patients with PD (BL, 2‐, 4‐, and 6‐year follow‐up [FU]) and 96 healthy control patients (HCs; 2‐ and 4‐year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated. Results At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E‐selectin and ß 2 ‐integrin. In contrast, we found a reduction of markers of the plasminogen activation system, eg, urokinase plasminogen activator. Neurospecific markers indicated increased levels of peripheral proteins of neurodegeneration and inflammation, such as fibroblast growth factor 21 and peptidase inhibitor 3. Several markers, including interleukin‐6 and cystatin B, correlated with cognitive decline and progression of motor symptoms during FU. These findings were independently validated in the Parkinson Progression Marker Initiative. Conclusions We identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.