Parkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative disorders characterized by long preclinical phases, during which molecular alterations occur well before the onset of overt clinical symptoms. Early detection is critical as it enables timely intervention, potentially slowing disease progression and improving patient outcomes. Recent advances in plasma proteomics have established validated approaches that capture organ-specific molecular alterations by selecting plasma proteins enriched in organ-specific mRNA expression profiles.
This project aims to utilize this validated approach to develop organ-specific proteomic scores tailored specifically for PD and AD. Initially, we will use established diagnostic cohorts from AMP-PD and AMP-AD to derive and validate disease-specific proteomic scores. We will identify proteins enriched in the brain and other organs implicated in the pathology of PD and AD, thereby creating disease-specific organ proteomic signatures.
Subsequently, we will apply these derived proteomic scores to longitudinal plasma proteomic data from the UK Biobank to determine the timing at which scores become elevated prior to clinical diagnosis of PD and AD. We will also compare the predictive performance and specificity of PD-specific and AD-specific proteomic scores to examine the distinctiveness and potential overlap of molecular changes in these two diseases.
The scientific rationale of this study is that organ-specific proteomic scores may serve as minimally invasive biomarkers for the early detection of PD and AD. This approach has significant potential to enhance early diagnostic capability, facilitate preventive interventions, and provide deeper insights into the unique and shared biological mechanisms underlying these major neurodegenerative diseases.
