It may be painful, but there could be an unusual upside to appendicitis: Those who have had their appendix removed are 20% less likely to develop Parkinson's disease, according to a new analysis of more than 1 million people in Sweden.
The tiny organ, which is attached to and opens into the lower end of the large intestine, may contribute to this brain disorder that affects nearly a million Americans, the researchers say. Their study was published Wednesday in the journal Science Translational Medicine.
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"Parkinson's disease is multisystem disorder," said Viviane Labrie, senior author of the study and an assistant professor at the Van Andel Research Institute in Michigan. "And so there's likely to be many sites of origin in terms of where Parkinson's disease starts, the [gastrointestinal tract] being one of them. For other people, it may begin in the brain."
'Not just a movement disorder'
Parkinson's disease is not only common, with 60,000 new diagnoses each year, it is also incurable. Symptoms include tremors or shaking of the fingers, hands, legs or feet; stiffness; difficulty balancing; depression; and gastrointestinal disturbances including constipation. Research has shown that gastrointestinal symptoms can begin up to 20 years earlier than movement symptoms.
"In the last decade, it's become evident that Parkinson's disease is not just a movement disorder," Labrie said in a podcast. One of the most common non-motor symptoms of Parkinson's is gastrointestinal tract issues, so some scientists believe the disorder might begin there, she said. In fact, the appendix contains a protein, alpha-synuclein, that is known to accumulate or clump together in the brains of Parkinson's patients, she noted.
Searching for connections between Parkinson's and the appendix, Labrie and her colleagues analyzed medical data for 1.6 million people in Sweden. This general population survey showed that having an appendectomy is linked to a 19.3% reduced risk of developing Parkinson's disease, according to the researchers.
Separately, they examined the records of 849 Parkinson's patients and found that an appendectomy was associated with delayed onset of the disorder by 3.6 years, on average.
"Alpha-synuclein is a protein that doesn't like to stay put. It's able to move from neuron to neuron, and it has been shown that it can travel," Labrie said. Potentially, the protein can travel up the vagus nerve connecting the gastrointestinal tract and the brain.
"If it were to enter the brain, it can seed and spread from there and have neurotoxic effects that could eventually lead to Parkinson's disease," she said.
The study earned applause from some and criticism from others.
Do not get an appendectomy to ward off Parkinson's, experts say
James Beck, chief scientific officer of the Parkinson's Foundation and an adjunct associate professor in the Department of Neuroscience and Physiology at New York University School of Medicine, said the new study is "solid."
Although the research shows that the disorder "may start in the gut," he said, "it is not an indication that people should get an appendectomy if they're worried about Parkinson's."
Beck, who was not involved in the study, said it lays the foundation for more research into other contributors to Parkinson's disease, including environmental factors. At the same time, he said, the research raises questions such as, are people having bad gastrointestinal illness that may lead to proteins leaving the gut and getting into the brain?
Overall, finding a link between the appendix and Parkinson's is significant, he said. "Understanding where that 20% is coming from could be useful in the bigger scheme of things for all people with Parkinson's disease," Beck said.
Kevin McConway, emeritus professor of applied statistics at the Open University in the UK, told the Science Media Centre that the study is "competent," yet he also had a criticism based on the researchers' use of statistics.
"People who had their appendix removed in early life will, on average, differ from people who didn't, in several ways," said McConway, who was not involved in the research. "Any of these differences might be the cause of the decreased risk of Parkinson's disease in those who had their appendix out, rather than the removal of their appendix."
He said that it's "not the case that cause and effect has been established beyond doubt" by the study.
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