Identifying Blood Proteomic Markers of Parkinson's Disease Dementia Using High-Throughput Approaches

INTRODUCTION: Parkinson's disease (PD) presents with motor and non-motor symptoms, including dementia, but the severity and rate of cognitive decline are heterogeneous and difficult to predict clinically. METHODS: We quantified baseline serum proteins with the high-throughput SomaScan(R) assay in 834 PD individuals and performed Cox regression to identify proteins associated with subsequent development of dementia. Candidate biomarker proteins were replicated in 371 individuals from an independent cohort and meta-analysed. RESULTS: Protein targets significantly associated with progression to dementia were predominantly involved in synaptic plasticity, protein degradation/lysosomal function and extracellular matrix organisation. Mendelian Randomisation further revealed that changes in the Nogo receptor RTN4R may be causally associated with the development of Lewy body dementia. DISCUSSION: We identified several proteins predicting progression to dementia in PD, indicating changes in blood proteome that precede the development of clinical symptoms by several years, providing a window of opportunity to identify at-risk individuals early on.