New Perspectives on Parkinson's Disease Subtyping: A Narrative Review.

Parkinson's disease (PD) is a complex neurodegenerative disorder that is heterogeneous in both its pathophysiology and clinical presentation. Genetic, imaging and biochemical biomarkers not only provide innovative, objective ways to subtype PD but also offer new insights into the underlying pathophysiology, revealing potential therapeutic targets and improving predictions of clinical phenotype, disease progression and treatment response. In this review, we first summarize the phenotypes linked to key PD genes - such as SNCA, LRRK2, GBA and PRKN - highlighting, for instance, that GBA-PD is often associated with prominent nonmotor features. We then explore studies that have defined new robust subtypes with imaging biomarkers, particularly T1-weighted MRI brain atrophy patterns, and their clinical implications. We also review the role of blood, CSF and urine biomarkers for monitoring disease progression and predicting its presentation in various domains (motor, cognitive, autonomic, psychiatric). These findings could have practical implications by guiding clinicians to individualize symptomatic treatment and helping researchers improve clinical trial design and recruitment, thus bringing us closer to the discovery of effective disease-modifying therapies.