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Review
. 2023;13(3):297-309.
doi: 10.3233/JPD-225111.

Proposal for a Biologic Staging System of Parkinson's Disease

Lana M Chahine  1 , Kalpana Merchant  2 , Andrew Siderowf  3 , Todd Sherer  4 , Caroline Tanner  5 , Kenneth Marek  6 , Tanya Simuni  7
Affiliations
Review

Proposal for a Biologic Staging System of Parkinson's Disease

Lana M Chahine et al. J Parkinsons Dis. 2023.

Abstract

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 α-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.

Keywords: Parkinson’s disease; alpha-synuclein; biomarkers; disease staging.

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Conflict of interest statement

The authors report no financial disclosures or conflicts of interest concerning the research related to the manuscript.

Tanya Simuni is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review.

Figures

Fig. 1
Fig. 1
Illustration of putative relationship between asyn aggregation, dopaminergic dysfunction, and clinical manifestations as represented in a biologic staging system for PD. Curve shapes, slopes, and their temporal relationship are qualitative and hypothetical. Time of PD Diagnosis signifies diagnosis based on current clinical diagnostic criteria, which in the proposed staging system will be redefined to the time of onset of the biological changes. In future versions of the staging system these curves will be shaped by data emerging from longitudinal studies.
Fig. 2
Fig. 2
Promising categories of biomarkers that may inform future versions of a biologic staging system for PD.
See this image and copyright information in PMC

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