The spread of pathological alpha-synuclein (aSyn) from the gastrointestinal tract to the brain, or the brain to the intestine, is of increasing interest given observations in experimental models. While there has been a focus on neuronal-mediated spread and propagation, non-neuronal reservoirs of aSyn are also present. In this issue, Yang et al describe the ability of extracellular vesicles, derived from red blood cells in circulation to mediate the deposition of aSyn into the GI tract. These vesicles may therefore represent a potential non-neuronal pathway by which aSyn may spread across body sites in the initiation and progression of Parkinson’s disease and other synucleinopathies.