SNCA and Parkinson disease: The discovery, in the 1980s, of alpha-synuclein deposits in the enteric nervous system (ENS) of PD patients136, and subsequent observations that constipation and alpha-synuclein deposits in gastrointestinal biopsies can predate the diagnosis of PD by decades, as well as the marked peripheral autonomic nervous system imaging abnormalities with relative sparing of the nigrostriatal dopaminergic system in patients with prodromal PD (isolated RBD)137–140 have implicated the gut as a possible site of origin in PD.