Does Parkinson Disease Begin in the Gut?

Parkinson disease (PD) is characterized by Lewy bodies composed of α-synuclein in the brain. Similar to what happens in prion diseases, “pathological” α-synuclein induces “healthy” α-synuclein (the normal protein) to misfold into a pathological shape. In recent years, autopsy studies have suggested that Lewy bodies first appear in the vagus nerve and then spread to the brain, promoting the idea that pathological α-synuclein is produced first in the gut and then moves retrograde up the vagus nerve to the brain.

Investigators synthesized pathological α-synuclein fibrils and injected them into the muscularis layer of the duodenum and pylorus of mice. The α-synuclein first appeared in the vagus nerve, then in the hindbrain, and ultimately in the…