Parkinson’s disease (PD) is a late onset neurological condition characterized by impaired movements: tremors, rigidity, slow movements, and abnormal posture. In recent years, numerous non-motor symptoms, including psychiatric, sleep, smell, and digestive alterations, have been identified as integral components of the disease. Loss of smell and constipation can appear a decade before the full motor symptoms, inviting arguments about the nature and origin of PD. Some argue that PD is caused by toxins that start the disease in exposed tissues (gut and olfactory epithelium) followed by spread to the brain areas that control movement. Alternative explanations include the sporadic development of toxic protein aggregates in multiple vulnerable neurons (multifocal). These aggregates can spread by neuronal networks to cause motor symptoms and multiple late complications. This paper discusses the merits of each hypothesis, which are a critical tool to better understand PD and, eventually, develop disease-modifying therapies. (By Dr. Pedro Fernandez-Funez, https://jmg.bmj.com/content/early/2019/09/03/jmedgenet-2019-106210 )