Share on Pinterest
Researchers are learning more about how Parkinson’s disease may be related to the gut. Getty Images

Could having your appendix out be the culprit behind Parkinson’s disease? Not quite, but there’s a link between the two, research finds.

The largest study to date on the relationship between appendectomies and Parkinson’s disease finds that people who had the procedure were more likely to develop the disease. But that doesn’t prove that appendix removal is a cause for Parkinson’s disease.

The research was introduced last week initially and will be presented fully at Digestive Disease Week on May 20.

Recent research into the cause of Parkinson’s disease has been focused on alpha-synuclein. That’s a protein found in the gastrointestinal tract of people who have early onset of the disease.

Previous research hasn’t been consistent about the link between appendix removal and Parkinson’s disease. Some studies don’t show any affiliation. A recent study out of Europe showed patients who still had their appendix were more likely to develop the disease.

A team led by Dr. Mohammed Z. Sheriff, lead author of the study and a physician at Case Western Reserve University, assessed more than 62.2 million patient records from 26 health systems in America. They looked at those who had appendectomies and were diagnosed with Parkinson’s disease at least six months later.

Of 488,190 patients, 4,470 — 0.92 percent — developed the disease. Of 61.7 million patients who didn’t have an appendectomy, 177,230 — 0.29 percent — later developed the disease. Patients who had appendectomies were three times as likely to develop Parkinson’s disease compared to those who didn’t. The research will be presented at Digestive Disease Week 2019.

The researchers say there were similar risk levels across all age groups regardless of race or gender. They couldn’t tell how much time passed after the surgery until the person was diagnosed with the disease.

While it shows a relationship between appendix removal and Parkinson’s disease, it’s only an association, Sheriff said. More research would be needed to confirm and understand the connection, he said in a statement.

“We do not definitively know the cause of Parkinson’s disease,” said James Beck, PhD, chief scientific officer of the Parkinson’s Foundation.

The protein called alpha-synuclein is linked to Parkinson’s disease, but the medical community isn’t certain what sets the process in motion of misfolding of this protein that leads to cell death, he told Healthline.

There are two main sources of alpha-synuclein in the body: at nerve terminals where nerve cells talk to each other and in red blood cells, Beck explained. The number of neurons in the gut rivals the number in the brain, and like the brain, a lot of blood flows through the gut.

“I think the misfolding of alpha-synuclein is at the heart of Parkinson’s disease. How that happens, or what is the triggering event, is currently anybody’s guess,” Beck said. “This is why basic research remains a critical area of investment for this disease.”

Dr. Rebecca Gilbert, chief scientific officer of the American Parkinson Disease Association, said that in rare cases families can pass on particular mutations of this protein.

“We know that rare families with particular mutations of alpha-synuclein — that cause the production of too much alpha-synuclein or abnormal alpha-synuclein — develop Parkinson’s disease,” explained Gilbert. “We also know that alpha-synuclein is the major component of the Lewy body, clumps found in the nerve cells of most people with Parkinson’s disease, and not just those with alpha-synuclein mutations. Beyond that, there remains much debate about the exact role of alpha-synuclein and the Lewy body in the development of Parkinson’s disease.”

Patients with the disease have nerves that line the gut, which includes the appendix. They control gut function and often contain structures that are like Lewy bodies. A Lewy body is an abnormal aggregate of protein that develops inside nerve cells and contributes to the disease. It’s well-known that gastrointestinal symptoms can occur in patients with the disease decades before onset of brain symptoms. One theory is that Lewy body pathology travels from the gut via the vagus nerve into the brain.

One theory about how the whole process starts is that a foreign substance that enters the body through the gut and induces the first alpha-synuclein molecule to take the wrong form, which causes the alpha-synuclein to aggregate and form a Lewy body. It’s not a proven theory. And how the appendix specifically is involved in these processes isn’t known. But the organ is a part of the gut that harbors immune cells that defend against microbes coming from the environment.

“The appendix, therefore, more than other parts of the gut, may have access to foreign substances that could enter and induce Lewy body formation, although more research is necessary to fully determine if this is what occurs,” Gilbert told Healthline.

Beck isn’t sure what mechanism is responsible for the link between appendix removal and disease development. Organ removal may not play a role in disease development at all, he noted.

“That said, an appendectomy is often the result of an appendicitis, that is a dangerously inflamed or ruptured appendix. So it may be that this inflammation, and the body’s subsequent response, may [create] the correct conditions that lead to misfolding of alpha-synuclein and eventually, maybe, Parkinson’s disease,” he said. “Think of it as getting a scratch in the paint of your car… the scratch will not always lead to rust, but it sets the stage for it to occur if the conditions are right.”

An appendix is only removed if there’s appendicitis, or inflammation of the appendix. Without treatment, the appendix could rupture and cause life-threatening infection. Appendectomy is therefore not an elective procedure, and the decision to have one isn’t under a person’s control.

“Whether or not you have had an appendectomy, your best bet is to focus on issues of brain health that are under your control, like increasing your exercise,” Gilbert said.

An epidemiological study like this one doesn’t explain the mechanism behind the disease, but it could lead scientists in the right direction for additional studies. In the future, more research may be done to better understand what happens in the body involving the appendix that may lead to Parkinson’s disease.

That would likely center on the inflammatory response, Beck noted.

Although the study showed a three-fold increase in disease development following an appendectomy, the shift was less than 1 percent. Even with an appendectomy, Parkinson’s disease is a rare event, Beck said.

The science behind this research is interesting and may guide the medical community to better understand Parkinson’s disease.

“But it’s nothing to worry about,” Beck added. “Do not fret if you had, or did not have, an appendectomy.”