Proposal for a Biologic Staging System of Parkinson's Disease

The Parkinson's disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from the earliest stages of pathology to manifest disease. Despite progress, a biologically based PD staging system does not exist. Such staging would be a useful framework within which to model the disease, develop and validate biomarkers, guide therapeutic development, and inform clinical trials design. We propose that the presence of aggregated neuronal alpha-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms identifies a group of individuals that have Lewy body pathology, which in early stages manifests with what is now referred to as prodromal non-motor features and later stages with the manifestations of PD and related Lewy body diseases as defined by clinical diagnostic criteria. Based on the state of the field, we herein propose a definition and staging of PD based on biology. We present the biologic basis for such a staging system and review key assumptions and evidence that support the proposed approach. We identify gaps in knowledge and delineate crucial research priorities that will inform the ultimate integrated biologic staging system for PD.

Automated summary

The Parkinson's disease research field has made progress in understanding the disease's clinical features and identifying potential biomarkers, but a biologically based staging system is still lacking. This system would provide a framework for modeling the disease, developing biomarkers, guiding therapeutic development, and informing clinical trial design. This article proposes a biologically based staging system for Parkinson's disease, highlighting the presence of aggregated neuronal alpha-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms as key markers for Lewy body pathology and disease progression.