Parkinson's Disease May Start In the Gut, Appendix

Parkinson's disease has long been considered a disease of the brain, but research out Wednesday found it may start in the gut, specifically in the appendix, a tiny organ near the large intestine.

Using health registries in Sweden of some 1.7 million people followed for 50 years, and a second US dataset  of 849 people, researchers found that those who had their appendix removed in early adulthood generally saw their risk of developing Parkinson's disease cut by 19 percent. In rural areas of Sweden, where people may be more exposed to pesticides, which may play a role in Parkinson's, the effect was even greater: a 25 percent lower risk of developing Parkinson's.

In those that ultimately did develop Parknson's disease, the research found that the age of onset was delayed by an appendectomy on average by 3.6 years. Therefore, the researchers believe that the studies suggest that the appendix might be a tissue site that plays a role in the early events or initiation of Parkinson's disease."

Useless Organ

Often, the appendix is considered a useless organ, but researchers say it is a storage site for gut bacteria, is linked to immune response, and appears to be a gathering place for a key protein implicated in Parkinson's, known as alpha-synuclein.

People with Parkinson's suffer from gastrointestinal disorders like constipation at least 10 years before the disease's better known symptoms like tremors, stiffness, and poor balance appear. Researchers, after taking a closer look at the appendix, found that nearly everyone has signs of clumped up alpha-synuclein present in their appendix.

But not everyone goes on to develop Parkinson's, for reasons that still aren't well understood.

"We think that in rare events, if it (alpha-synuclein) were to escape the appendix and enter the brain, this could lead to Parkinson's disease," said study author Viviane Labrie. Experiments have shown the protein "can travel up the nerve that connects the G.I. (gastrointestinal) tract to the brain. And 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."

Researchers say it's possible that someday, drug therapies could be developed to cut down on the protein's accumulation in the appendix, thereby lowering the risk of Parkinson's. In the meantime, experts stressed they do not recommending that anyone go out and get an appendectomy to cut the risk of Parkinson's.

More research is needed to better understand the role that the appendix may play in Parkinson's disease.

Gut-Brain Connection

According to Kevin McConway, emeritus professor of applied statistics at The Open University, the study goes "part of the way to establishing a reason why the relationship between appendix removal and Parkinson's disease might be one of cause and effect."

Conway, who was not involved in the research, added that "several previous studies have looked for relationships between appendix removal and various other diseases, including heart disease as well as various diseases of the gut. For some of these diseases, having your appendix out was associated with a reduced disease risk, but in others, including heart disease, it was associated with an increased risk."

Indeed, a smaller study using Danish health registries, published in 2016, found that appendectomy was associated with a small increase in Parkinson's disease risk 10 or more years after surgery.

The latest findings represent the largest and longest-running study to date. Even though they may not offer the last word on the matter, they do bolster what scientists know about the close connection between the brain and the gut, which actually contains a lot of neurons that are linked back to the brain via the vagus nerve.

"Some scientists have called the intestine the second brain, because of the number of neurons that are present in there," said co-author Patrik Brundin, director of the Center for Neurodegenerative Science at Van Andel Research Institute.

What do you think about this research? Have you ever heard of this possible relation?