Appendix Removal Linked to 20% Drop in Parkinson’s Disease Risk

People who have their appendix removed at a young age appear to have a decreased risk of developing Parkinson’s disease later in life, scientists have found. The findings do not advocate the removal of the appendix as a preventative measure against Parkinson’s—instead, they highlight the role the gut might play in the degenerative disease.

Parkinson’s is a complicated disease that affects around 10 million people worldwide. Around 60,000 Americans are diagnosed with the disease every year. It is a neurodegenerative disorder, the cause of which is currently unknown. There is no cure—instead, symptoms are managed through various treatments.

In recent times, scientists have found increasing evidence to suggest Parkinson’s does not begin in the brain, but in the gut. A study published earlier this year found gut microbes promote the growth of the protein alpha-synuclein—which has been closely linked to the onset and progression of Parkinson’s.

In research published by Science Translational Medicine, an international team of scientists used data on 1.6 million people living in Sweden. They looked at appendix removal—including the age at which the operation took place—the instances of Parkinson’s and whether the person lived in an urban or rural environment. Previous research has indicated people living in rural locations are at greater risk of Parkinson’s, potentially because of the increased exposure to pesticides.

The findings showed that people who had their appendix removed at a young age had a 19 to 25 percent reduced risk of developing Parkinson’s. The higher risk reduction was seen in people living in rural areas. Researchers found that appendix removal delayed the progression of Parkinson’s in people who later went on to develop it by an average of 3.6 years.

parkinsons appendix risk Aggregated alpha-synuclein in the neurons of the appendix. Courtesy of Van Andel Research Institute

The data did not appear to show appendix removal was linked to a lower risk of Parkinson’s where a person was genetically predisposed to the disease. Removing the appendix after the onset of Parkinson’s also had no effect on the progression of the disease.

Researchers also found the appendix serves as a major reservoir of abnormally folded alpha-synuclein proteins. Clumps of this protein were previously thought to be a hallmark of Parkinson’s—but the team found it in the appendixes of healthy people of all ages.

"Our results point to the appendix as a site of origin for Parkinson's and provide a path forward for devising new treatment strategies that leverage the gastrointestinal tract's role in the development of the disease," said Viviane Labrie, from the Van Andel Research Institute and senior author of the study. "Despite having a reputation as largely unnecessary, the appendix actually plays a major part in our immune systems, in regulating the makeup of our gut bacteria and now, as shown by our work, in Parkinson's disease."

The study has generally been welcomed by experts working in the field, but more work will be needed to show the exact relationship between the appendix and Parkinson’s. Charbel Moussa,  director of the Translational Neurotherapeutics Program at Georgetown University Medical Center, told Newsweek the data are “fascinating” but does not show which way the pathology moves—from gut to brain or brain to gut. “This study describes a phenomenology but falls short of explaining where the pathology starts and where it ends in Parkinson's.

parkinson's symptoms Symptoms of Parkinson's Disease iStock

"Epidemiological studies have shortcomings and it would be great if the evidence was that cleaved fragments of alpha-synuclein were found in the appendix prior to onset of Parkinson’s Disease. That would suggest a temporal relationship. The study shows that normal individuals and [Parkinson's] patients have lots of alpha-synuclein in the appendix but it would be more conclusive if the cleaved species were at least associated with the timeline of onset and progression of [the disease]."

David Standaert, from the Department of Neurology the University of Alabama at Birmingham, said it was an important new study.

“The size of this study is impressive, as is the attention to detail, and overall I find it convincing,” he told Newsweek. “They also offer a biological explanation, suggesting that the appendix may be a source of abnormal synuclein that eventually spreads to the brain.

“I think the most important thing to recognize here is that while this study shows an association, that is not the same as establishing causation. All of the patients in the study had an appendectomy for a reason—most likely either appendicitis, or removal of the appendix during surgery for another problem [a common surgical practice]. It is possible that whatever factors, genetic or environmental, that led these patients to have an appendectomy also reduced their risk for [Parkinson’s], but the appendix was not directly involved in the [disease] process. Even if there is causal connection, the idea that the appendix is the source of abnormal synuclein that reaches the brain is still mostly speculation.”

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