Revisiting Parkinson's disease definition and classification: insights from two emerging biological frameworks

Area of Science:

• Neuroscience
• Genetics
• Biomarker Research

Background:

• Parkinson's disease (PD) is a complex neurodegenerative disorder with varied clinical and genetic profiles.
• Misfolded alpha-synuclein aggregates forming Lewy pathology are central to PD pathogenesis.
• Advances in biomarkers and genetics are driving biologically informed PD classification and staging.

Purpose of the Study:

• To review and compare two emerging frameworks for classifying and staging Parkinson's disease: SynNeurGe criteria and NSD-ISS.
• To highlight the differences in scope, definitions, and applications of these biologically grounded PD models.
• To discuss ongoing challenges in refining and implementing these frameworks for PD research and clinical practice.

Main Methods:

• Review of the SynNeurGe criteria, incorporating synucleinopathy, neurodegeneration, genetic risk, and clinical status.
• Analysis of the Neuronal α-Synuclein Disease Integrated Staging System (NSD-ISS), focusing on molecular markers, dopaminergic dysfunction, and genetic anchors.
• Comparative assessment of the principles, operational definitions, and implementation strategies of both frameworks.

Main Results:

• SynNeurGe classifies PD subtypes across the disease spectrum, acknowledging clinical heterogeneity.
• NSD-ISS defines neuronal α-synuclein disease using specific biomarkers and stages progression.
• Both frameworks aim to improve early detection and PD research but differ significantly in their approach and scope.

Conclusions:

• These frameworks represent a significant shift towards biologically defined Parkinson's disease concepts.
• Challenges remain in mechanistic understanding, biomarker standardization, genetic diversity, and ethical considerations.
• Continued refinement, validation, and equitable implementation are crucial for the success of these biologically based PD models.