The research, which looked at more than 1.6 million patient records, found people who had their appendix removed were 19 per cent less likely to develop the condition, and those that did get Parkinson's were diagnosed an average of 3.6 years later.
One of the more quizzical findings: people living in rural areas who underwent appendectomies appeared to benefit most from the reduced risk.
"There's potential for [gastrointestinal]-tract based therapies that could block the formation and spread of alpha-synuclein clumps as future, early, and preventative treatments for Parkinson's disease", professor Viviane Labrie from the Center for Neurodegenerative Science at the Van Andel Research Institute in MI said in a press teleconference.
The findings also solidify the role of the gut and immune system in the genesis of the disease, and reveal that the appendix acts as a major reservoir for abnormally folded alpha-synuclein proteins, which are closely linked to Parkinson's onset and progression.
Knowing that people with Parkinson's also suffer from gastrointestinal disorders like constipation at least 10 years before the disease's better known symptoms like tremors, stiffness, and poor balance surface, researchers chose to take a closer look at the appendix and its potential role. People with Parkinson's disease have clumps in their brains called "Lewy bodies", which contain substances including alpha-synuclein.
It noted that "the human appendix contains an abundance of misfolded a-synuclein" and that "removal of the appendix decreased the risk of developing" the disease. It is possible for alpha-synuclein to travel from the gastrointestinal tract via the vagus nerve and reach the brain.
According to Labrie, the main difference is that her study spanned 52 years of follow-up, "which allowed us to see the lowered risk of an appendectomy on Parkinson's disease risk", compared to the Danish study, which lasted about three decades.
One of the United States study's professors Bryan Killinger said: "Our findings today add a new layer to our understanding of this incredibly complex disease".
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She's a neuroscientist with the Center for Neurodegenerative Science at the Van Andel Research Institute in Grand Rapids, Mich. This builds on previous research indicating that, for some, Parkinson's starts in the gut. The team analysed 847 people with Parkinson's disease as well.
The findings suggest that the appendix "might be important in the early events or possibly in the initiation of this disease", said senior author Viviane Labrie, an assistant professor of neuroscience at Van Andel Research Institute in MI.
The research could, however, help lead to better treatments or preventative measures for the disease, and generally better help doctors understand it. "And we think only in rare instances would it be able to accumulate excessively and escape the appendix and potentially enter the brain and cause Parkinson's disease". "Inflammation has been linked to Parkinson's disease and the appendix is actually an immune tissue that is responsible for the sampling and monitoring of pathogens, and will raise immune responses", Labrie says.
Data for the study were gleaned from an in-depth characterization and visualization of alpha-synuclein forms in the appendix, which bore a remarkable resemblance to those found in the Parkinson's disease brain, as well as analyses of two large health-record databases.
That kind of study doesn't prove that removing the appendix is what reduces the risk, cautioned Dr. Andrew Feigin, executive director of the Parkinson's institute at NYU Langone Health, who wasn't involved in Wednesday's research.
Instead, Labrie said more research is needed to find ways to control the rogue protein.
"Understanding where and how Parkinson's begins will be absolutely crucial to developing treatments that can stop it and potential prevent it altogether".
Claire Bale, head of research at Parkinson's United Kingdom, said: "There is much still to learn about how surgical approaches, such as removing the appendix, may stop the progression of toxic proteins that cause Parkinson's".
But the hunt for the origins of Parkinson's still can not explain why the disease develops in some people but not others.