Withdrawal from the appendix is ​​linked to a lower risk of Parkinson's disease

Scientists have discovered a new clue that Parkinson's disease may not originate in the brain but in the intestines – perhaps in the appendix.

Researchers whose appendix had been removed early in life were less likely to contract brain disease causing tremors decades later, researchers said Wednesday.

Why? A look at the surgically removed appendicular tissue shows that this tiny organ, often considered useless, appears to be a deposit for an abnormal protein – an organ that, if it manages to penetrate the brain, becomes a distinctive sign of Parkinson's disease.

The big surprise, according to studies published in the journal Science Translational Medicine: Many people can house clumps of this worrying protein in their appendix – young and old, people with healthy brain and those with Parkinson's disease.

But do not look for a surgeon for the moment.

"We are not saying to go do an appendectomy," said Viviane Labrie of the Michigan Van Andel Research Institute, neuroscientist and geneticist who led the research team.

After all, many people who do not have an appendix are still developing Parkinson's disease. And many others feed the protein responsible but never get sick, according to his research.

THE GUT CONNECTION

Doctors and patients have long known that there is a link between the gastrointestinal tract and Parkinson's disease. Constipation and other gastrointestinal disorders are very common years before patients experience tremor and movement difficulties leading to Parkinson's diagnosis.

Wednesday's research promises to revitalize work to find out why and who is really at risk.

"It's an excellent piece of the puzzle. This is a fundamental clue, "said Dr. Allison Willis, a Parkinson's disease specialist at the University of Pennsylvania, who did not participate in the new studies, but says her patients routinely ask her questions about the disease. instinctive link.

Parkinson Foundation Chief Scientist James Beck, who was not involved either, agreed that there are many fascinating potential links. "

He noted that despite its reputation, the appendix appears to play a role in immunity that could affect intestinal inflammation. The type of bacteria living in the intestines can also affect Parkinson's disease.

But while it's very common to harbor this protein linked to Parkinson's disease, "what we do not know is what triggers it, which makes things happen," Beck said.

For years, scientists have speculated on what could cause the bowel-Parkinson link. One main theory: maybe a bad protein "alpha-synuclein" can move nerve fibers in the gastrointestinal tract to the vagus nerve, which connects the body's major organs to the brain. An abnormal alpha-synuclein is toxic to the brain cells involved in the movement.

There have been previous clues. People whose vagus nerve had been severed as part of a now-discontinued therapy had a reduced risk of Parkinson's disease. Some smaller studies have suggested that appendectomies could also be protective – but the results were contradictory.

Labrie's team set out to find stronger evidence.

First, the researchers analyzed Sweden's huge national health database and examined the medical records of nearly 1.7 million people monitored since 1964. The risk of developing Parkinson's disease was 19% higher. low in those whose appendix had been removed surgically decades ago.

A confusing warning: people living in rural areas seemed to benefit. Labrie said that it was possible that the appendix plays a role in the environmental risk factors of Parkinson's disease, such as exposure to pesticides.

Further analysis suggested that people who developed Parkinson's disease despite early appendectomy in their lifetime tended to have symptoms a few years later than patients of the same age.

A common protein

This type of study does not prove that removing the appendix is ​​what reduces the risk, warned Dr. Andrew Feigin, executive director of the Parkinson's Institute at NYU Langone Health, who had not participated in Wednesday's research.

Then, Labrie's team examined the appendiceal tissue of 48 people without Parkinson's disease. In 46 of them, the appendix contained the abnormal protein linked to Parkinson's disease. It was the same for some patients with Parkinson's. Whether the appendix is ​​inflamed or not does not matter.

This is a crucial discovery because it means that simply holding the protein in the intestine is not enough to trigger Parkinson's disease, Labrie said. There must be another step that makes it dangerous only for some people.

"We think the difference lies in the way you manage this pathology," she said, "how does the body handle accumulation?"

His team is planning more studies to do.

The discovery of the reservoir is compelling, said Feigin, but another key question is whether the abnormal protein is also collected in the intestines of healthy people.

And Penn's Willis adds another caveat: There are other risks not related to Parkinson's disease, such as traumatic brain injury.

"This could be one of the many pathways that lead to Parkinson's, but it's very exciting," she said.

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