Proteomic analysis of Parkinson’s disease patient cohorts show similarities in mechanism to Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s Disease and Parkinson’s Disease (PD) share similarities in phenotype and an overlap between disease subtypes and diagnostic testing which implies a link between some of the neurodegenerative processes.Here, we report the initial results for proteomic assays on two longitudinal PD cohorts demonstrating dementia‐like protein dysregulation signatures as well as PD specific signatures in the largest proteomics collection of PD patients to date.MethodWe used aptamer‐based technology (SOMAmer assay, SomaLogic®) to measure 4003 proteins in 1599 serum samples collected from two observational longitudinal cohorts: Oxford Parkinson’s Disease Centre Discovery cohort (OPDC) and the UK Tracking Parkinson’s cohort. Clinical measures of disease progression included the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III (UPDRS) and Montreal Cognitive Assessment (MoCA) adjusted for education years. The sample set included 319 controls.We performed dysregulation analysis on log2 transformed data using linear models corrected for age, gender, and cohort. Enrichment analysis was implemented in the R library clusterProfiler using the KEGG and GO databases. Comprehensive co‐expression analysis was performed using WGCNA.ResultInitial pathway analysis showed that the main significantly dysregulated protein pathways of case status were the Complement and coagulation cascades (p = 0.0086) and Protein digestion and absorption (p =0.0152). The Fat digestion and protein absorption pathway was enriched for dysregulated proteins associated to the UPDRS measure (p = 0.00142). Using co‐expression analysis we identified a module of 625 proteins with a significant relationship to disease status (p = 3.20x10‐07) and the movement (p = 2.35 x10‐05) and cognition (p = 0.005) endophenotypes. This module was enriched for proteins involved in axon guidance in addition to the complement and coagulation cascades and protein digestion and absorption found in initial analyses.ConclusionUsing a comprehensive profiling analysis of protein expression in two unique longitudinal PD cohorts we demonstrate the overlap between neurodegenerative disease types as well as highlight unique PD associations with potential mechanistic links to gut processes. This will have implications for further analysis of these PD cohorts for further mechanistic analysis and more importantly biomarker detection.