Fig. 7.

Schematic overview of the hypothesized trans-synaptic bidirectional propagation of asyn pathology through the autonomic nervous system to the brain after gastrointestinal seeding. First, seeding of the duodenum with fibrils induces aggregation of endogenous asyn in the duodenum. Second, the induced pathology retrogradely spreads along the parasympathetic pathway to the dorsal motor nucleus of the vagus (DMV) and along the sympathetic pathway to the celiac ganglia (CMG). Third, asyn pathology propagates trans-synaptically to the locus coeruleus (LC) and intermediolateral nucleus of the spinal cord (IML). Additionally, asyn pathology spreads anterogradely to the heart and to the stomach. Fourth, asyn pathology spreads to the substantia nigra pars reticulata (SNr)