Recently, two proposals for defining Parkinson's disease and its related pathogenic processes have been published. In this viewpoint, we discuss the primary drivers behind these efforts, the future directions, and the challenges that must be addressed. While finding biomarkers is a mandatory step for better precision medicine and optimal patient stratification in therapeutic trials, we argue that a biological definition of Parkinson's disease based on a single biomarker will struggle to account for the complexity of the mechanisms involved in developing the disease. Additionally, a biological definition of asymptomatic patients should rely on a thorough understanding of patients' clinical trajectories, which is currently not the case in synucleinopathies.
Keywords: Parkinson's disease; biomarkers; neurodegeneration.
Two recent articles proposed a biological definition of Parkinson's disease, highlighting the importance of detecting aggregated alpha-synuclein in biofluids or tissues. This viewpoint explores the motivations behind these proposals, their potential implications, and the challenges they face. It emphasizes that relying on a single biomarker to define Parkinson's disease is unlikely to capture its complexity. The authors advocate for combining clinical and biological insights. They also discuss parallels with Alzheimer's disease and how similar approaches influenced its diagnosis and therapeutic development.