Does Parkinson’s disease (PD) begin in the gut? Some neurology researchers speculate that the misfolding of alpha-synuclein proteins—which appear to play a major role in the etiology of PD—may originate in the autonomic nerve terminals of the gastrointestinal tract. The hypothesis is that alpha-synuclein pathology, found in Lewy body deposits, may initiate from outside the central nervous system (CNS) and then use the vagus nerve as a route to the brain.
One piece of evidence for this hypothesis is that alpha-synuclein inclusions have been found in gastrointestinal nerve endings up to 20 years before PD diagnosis in some patients. Furthermore, gastrointestinal symptoms are among the most common non-motor symptoms of PD, but may occur years or even decades before observable motor symptoms.
If this hypothesis is true, then would severing the vagus nerve—the route between the gut and the brain—reduce the risk of PD? A recent study investigated this question.
Researchers in Sweden used nationwide registries to identify 9,430 people who had a vagotomy for peptic ulcer, and compared them with 377,200 people from the general population. The results showed that people who had a truncal vagotomy (but not a selective vagotomy) were 40% less likely to develop PD after five years than those who had not had any vagotomy.
In this interview, study author Karin Wirdefeldt, MD, PhD, discusses the ideas behind this study and how the findings may support the prevention of Parkinson’s disease.
MDLinx: What evidence led you to investigate the association between vagotomy and PD?
Dr. Wirdefeldt: In the Parkinson’s disease brain, the pathology starts in the vagal nuclei and the olfactory bulb, and then spreads to the substantia nigra and other parts of the brain—a pattern that is correlated with progression of symptoms. Due to the early involvement of the vagal nuclei, it has been hypothesized that the pathology may start in the gut and spread to the brain stem via the vagus nerve.
MDLinx: What were the conclusions of your investigation?
Dr. Wirdefeldt: Our study provides preliminary evidence supporting a link between the gut and the brain in PD, but a lot more research is needed to better understand the mechanism.
MDLinx: Can you speculate why truncal vagotomy, but not selective vagotomy, was associated with a lower risk for Parkinson's disease?
Dr. Wirdefeldt: In a truncal vagotomy, the nerve trunk is fully resected, while in a selective vagotomy only some braches of the nerve are resected. Therefore, if the hypothesis that Parkinson’s disease pathology spreads via the vagal nerve is true, truncal vagotomy can block that route better than selective vagotomy.
MDLinx: Truncal vagotomy wouldn’t be a very practical way to prevent PD. Can you foresee any other potential preventive therapies that should be further investigated in light of the conclusions of this study?
Dr. Wirdefeldt: The exact mechanism and factors related to the misfolding and spread of alpha-synuclein remain unclear. Indeed, much more research is needed to develop preventive therapies for PD.
MDLinx: Are you now working on a follow-up study of this research?
Dr. Wirdefeldt: Yes, we do plan to follow up these results in further epidemiological studies, but it is too early to discuss the details.
About Dr. Wirdefeldt: Karin Wirdefeldt, MD, PhD, is a neurology researcher in the Department of Medical Epidemiology and Biostatistics and the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm, Sweden.