Pathological alpha-synuclein inclusions can be detected in the entire gastrointestinal tract as early as 20 years before the diagnosis of PD, supporting the Braak proposed model for the pathophysiology of alpha-synuclein aggregates in PD (Braak stage 1) and making constipation one of the earliest recognizable prodromal features (22, 24). This evidence concerns the gene SNCA and Parkinson disease.