The appendix, a miniature sac attached to the large intestine, is reputable for having no known function and occasionally needing to be cut out. Now, a study suggests that it could even be supplying a brain-damaging protein involved in Parkinson’s disease and that removing it early in life can decrease a person’s risk of the disease or delay it.
Parkinson’s disease is a progressive disease of the nervous system that primarily affects one’s movement, and the brain of a person with it usually contains clumps of a misfolded form of a protein known as α-synuclein (αS) which can damage and kill neurons. If the parts of the brain responsible for movement are harmed, the results could lead to some symptoms of Parkinson’s. Combined with information from past studies, this observation leads to a theory suggesting that dysfunctional αS spreads up the fibres of the vagal nerve, a nerve connecting the brain to the appendix, by converting healthy forms of the protein to misfolded, clumpy ones.
In this recent study, neuroscientist Viviane Labrie and her team at the Van Andel Institute in Michigan decided to focus on the appendix of a large population over a long time.
When analyzing samples for different forms of αS, they discovered that 46 out of 48 appendixes contained a clumped form of αS similar to that seen in the Parkinson’s brain. “It’s present in all of us,” Labrie says, “but appears to cause trouble only if it spreads to the brain”. The appendix may also be a breeding ground for this protein. When normal αS exposed to the contents of healthy appendix tissue cells, the proteins were cleaved into a shorter form. This makes them more prone to aggregation, and perhaps more likely to spread to the brain.
Moreover, they found that there is around a 1% chance that a person will develop Parkinson’s after age 65, but for those who had an appendectomy (a surgical removal of the appendix), the risk of developing the disease was about 20% lower. The onset of Parkinson’s was delayed by roughly 3.6 years in patients who had an appendectomy 20+ years prior to their diagnosis.
In addition, when the researchers classified the population into rural and urban residents, the benefit of an appendectomy was only observed for the rural group. According to Labrie, that’s a clue that an appendectomy might be most useful in cases that Parkinson’s disease has some environmental trigger.
However, if an appendectomy occurred closer to the diagnosis, the onset of the disease was not delayed by much. “When we get rid of [the appendix], you are safe for a few years, but then it just starts somewhere else in the gut,” says Borghammer, a neuroscientist at Aarhus University in Denmark, who was not involved in the study. Also, the study found that an appendectomy didn’t protect people with one of the inherited genetic mutations strongly linked to Parkinson’s.
Due to all this uncertainty, Labrie is saying that “preventive surgery is too far,” but she and her team hope future Parkinson’s treatments may take their research into account. As for now, they’re searching for other differences between the appendix of a healthy person and a person with Parkinson’s to explain how and when αS protein may cause problems.
For more about this breakthrough research, read the original article: https://www.sciencemag.org/news/2018/10/seeds-parkinson-s-disease-may-hide-appendix.
Image Credit: B. A. KILLINGER ET AL. SCIENCE TRANSLATIONAL MEDICINE (2018)
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