How Might the Appendix Play a Key Role in Parkinson’s Disease?

Most people forget they even have an appendix unless it bursts or becomes inflamed, but a new study suggests the organ may play a key role in the development of Parkinson’s disease. Those who have their appendixes removed in young adulthood run a nearly 20 percent lower risk of developing Parkinson’s decades later, according to a study published this week in Science Translational Medicine.

The new finding helps solidify the developing view Parkinson’s is not just a motor disorder characterized by tremors, stiffness and imbalanced walking—but a whole-body condition that often involves the digestive system, says lead author Viviane Labrie, an assistant professor at the Van Andel Research Institute’s Center for Neurodegenerative Science. The appendix is attached to the large intestine and houses gut bacteria, she notes. The fingerlike pouch of tissue, which used to be considered a useless vestige of our evolutionary past, is now believed to play an important role in immune function—particularly early in life. It is not yet known what initiates Parkinson’s, although a growing body of research suggests inflammation plays a key role, Labrie and others say.

The multipart study looked at a database of 1.6 million people in Sweden and found a lower risk of Parkinson’s among those whose appendixes had been removed, co-author Lena Brundin said Tuesday in a news conference. She added that the difference was particularly pronounced among people living in rural parts of the country—potential reasons for this remain unclear, although pesticide exposure has been shown to be linked to Parkinson’s, says Brundin, an associate professor at Van Andel, an independent research and science education organization in Grand Rapids, Mich.

The researchers also looked at a much-smaller database of about 850 people whose Parkinson’s has been carefully followed, and found those who had undergone appendectomies developed the disease 3.6 years later on average than those who still had an appendix. They also found the protein alpha-synuclein, which is misshapen in Parkinson’s patients, in the appendixes of 48 out of 50 healthy people—suggesting the protein may play a useful (but still unknown) function there. Patrik Brundin, who is associate director of research at Van Andel and director of its Neurodegenerative Science center, says he was surprised to find so much alpha-synuclein in healthy people, and also that the protein was equally abundant in both old and young study subjects. “Those are all, for boring scientists like us, sufficiently surprising to make us excited,” he says.

According to Labrie, deformed clumps of alpha-synuclein might travel up the vagus nerve, which connects the digestive system to the brain, and then seed the brain with this destructive protein. Clumps of it are thought to block the production of the chemical dopamine, causing the tremors and stiffness that define Parkinson’s.

Ole Isacson, a professor of neurology at Harvard Medical School who was not involved in the research, has a different view. He believes removing the appendix may help prevent or delay Parkinson’s by blocking inflammation, which he sees as the true bad actor. Inflammatory bowel disease and inflammation of the gut have been linked to Parkinson’s, and one recent study found treating inflammatory bowel disease patients with an anti-inflammatory called anti-tumor necrosis factor reduced their likelihood of developing Parkinson’s by nearly 80 percent. There are many causes of Parkinson’s, says Isacson, who also directs the Neuroregeneration Laboratories and Neuroregeneration Research Institute at McLean Hospital. But he notes “maybe half or more of the patients with Parkinson’s disease have had some kind of inflammatory condition that has accelerated that pathology.”

Malú Tansey, a professor of physiology at Emory University who did not take part of the study, agrees research into the connection between inflammation and Parkinson’s might eventually lead the way to treatments and better diagnosis. She says it is possible that avoiding inflammation in the gut—through good diet and exercise, medications or probiotics—might be protective against Parkinson’s.

Many people who develop Parkinson’s suffer earlier in their lives from constipation, loss of smell, low blood pressure and sleep disorders such as acting out their dreams, says Rachel Dolhun, a movement disorder specialist and vice president of medical communications for the Michael J. Fox Foundation, which supports Parkinson’s research. People should not be concerned if they have occasional constipation in midlife, she notes, but a constellation of these symptoms may mean someone is at higher risk for developing the disorder. She hopes people will eventually be able to get risk scores early enough to let them to make lifestyle or medication changes in attempt to prevent the disease, she says.

Both Dolhun and Labrie say people should not get their appendixes removed because of the new findings. A study like this can only identify an association—not a clear cause-and-effect relationship between appendix removal and reduced risk of Parkinson’s. “You wouldn’t want anybody to run out and get their appendix taken out just because that might lower their risk of Parkinson’s,” Dolhun says.