LAUSR

Parkinson disease (PD) was formally described by James Parkinson in the classic “An Essay on the Shaking Palsy” published in 1817.1 More than 200 years later, PD remains largely defined clinically according to a combination of motor and nonmotor symptoms. PD is a complex neurodegenerative disorder involving dysregulations in multiple neurotransmitter systems beyond dopamine, and studies continue to shed light on the molecular, genetic, and pathophysiologic aspects of the disease. Identifying different subtypes of PD has been an active area of research with promising prospects to improve the understanding of disease mechanisms, to predict prognosis, and ultimately to develop personalized disease-modifying therapies. Subtypes of PD have been defined according to clinical symptoms and demographic characteristics. However, data-driven clinical subtyping has failed to predict patterns of aggregation of α-synuclein2,3 and was found not to be stable over time or reproducible.4,5 Therefore, an alternative to subtyping patients with PD on the basis of co-occurring clinical symptoms is to identify biological-based subtypes, or biotypes, based on shared and distinguishable neuroanatomical signatures.