Initiation and Transmission of α-Synuclein Pathology in Parkinson's Disease

The pathogenesis of Parkinson's disease (PD) involves the accumulation of aggregated forms of α-synuclein in the body. The location for the initiation of misfolded forms of α-synuclein is now a contentious issue, what was once thought to be a disease of the central nervous system (CNS) now appears to involve multiple organs in the body. In particular, the two regions in the body where the nervous system is exposed to the environment, the olfactory bulb and the enteric nervous system, are now thought to play an important role in the initial phase of the disease. Epidemiological studies point to the gastrointestinal tract, including the appendix, as a potential site for the misfolding and transmission of α-synuclein, with the vagus nerve providing a conduit between the gut and brain. A growing body of animal studies also support this pathway, implicating the transmission of pathological α-synuclein from outside the CNS in the development of PD.