Defining the Riddle in Order to Solve It: There Is More Than One "Parkinson's Disease"

Area of Science:

• Neurology
• Neuroscience
• Genetics

Background:

• Parkinson's disease (PD) is a complex neurological syndrome with evolving definitions.
• Inconsistencies exist in clinical, genetic, and neuropathological characterizations of PD.
• These discrepancies hinder progress in understanding and treating distinct PD forms.

Purpose of the Study:

• To identify and address inconsistencies in the definition of Parkinson's disease (PD) and its variants.
• To lay the groundwork for a more unified approach to defining PD.
• To advocate for integrating diverse scientific disciplines for a comprehensive understanding of PD.

Main Methods:

• Task force identification of inconsistencies across clinical, neuropathological, and genetic domains.
• Review of existing criteria for PD characterization.
• Advocacy for systematic, evidence-based integration of disciplines.

Main Results:

• Current definitions of PD and its variants are inconsistent across clinical, neuropathological, genetic, biomarker, and mechanistic domains.
• A lack of alignment in operational definitions hinders progress.
• A need for a systematic and evidence-based integration of diverse disciplines is identified.

Conclusions:

• Defining endophenotypes of "typical PD" accurately is crucial.
• Better definition and stratification of PD variants are needed for therapeutic trials.
• Integration of disciplines is a prerequisite for breakthroughs in precision medicine for PD.