Is the appendix linked to Parkinson's Disease?

One thing that the medical literature is not quite clear about is whether having your appendix removed might put you at greater risk of developing Parkinson’s disease. One recent study - carried out in Denmark - found exactly that. But another - which was based on data from millions of people in Sweden and the US - claimed the opposite. So, what is going on, and what has Parkinson’s got to do with the gut in the first place? Here’s Claire Bale, associate director of research at Parkinson’s UK…

Claire - Parkinson's is a condition that causes people to have difficulties with their movement. So people will probably be familiar with people who shake, people who are very slow and stiff. So that's in a nutshell, what people think of as Parkinson's. And it's caused by cells in the brain that make a chemical called dopamine being slowly lost, damaged over time. Without that precious chemical, the messages that we need to control our movements cannot get through. And that leads to the physical symptoms, but it can also have many other symptoms that are not so obvious. So things like changes in mood, changes in sleep, changes in the gut as well, which we'll talk about a little bit more.

Chris - What are those gut issues? Because that's surfaced in more recent years, the association between other things changing around the body, including complaints in the intestinal system.

Claire - Yes, absolutely. So probably the most prominent gut issue that people with Parkinson's experience is constipation. Some studies estimate up to 90% of people with Parkinson's experience constipation and that this can actually precede their diagnosis. This has led to a lot of research looking at, well, what is going on inside the gut in Parkinson's? What could be at the root of this constipation problem? And we know now that there are changes in the gut microbiome in people with Parkinson's, so the bacteria that are living in the gut. This has also led to research looking at the nerves around the gut, which do have a connection directly into the brain and a theory that perhaps Parkinson's may start in the gut for some people with Parkinson's and travel up those nerves into the brain before it leads to the classic symptoms of Parkinson's. So yes, it's a hugely active area of research and I think there's still a lot of work to be done to clarify exactly how the gut is involved, but certainly it's an emerging and very important area of research.

Chris - Do the microbes go off kilter and then cause those symptoms and possibly transmit the problem into the brain? Or does something else cause things to change in the function of the intestine and that has a knock-on effect for the microbes and transmits the problem to the brain?

Claire - I think this is the question that we still don't know the answer to, but we do think that a protein called alpha-synuclein may be important here. So this is the protein that when you look inside the brain of someone with Parkinson's after they passed away, we almost always see clumps of sticky proteins called Lewy bodies. And a huge constituent of those Lewy bodies is a protein called alpha-synuclein, which misfolds, so becomes misshapen and toxic we believe, to the brain cells affected in Parkinson's. Now what some research is suggesting is that we can actually see that same protein becoming misfolded and misshapen in the nerves, in the gut, in people with Parkinson's, although we still need to do a lot more research into this. So perhaps something happens in the gut. It could be exposure to things in our environment. For example, toxins, environmental chemicals, pollution, who knows? Something causes changes in the gut, perhaps in the microbes in the gut, and that ultimately causes this trigger that causes alpha-synuclein to start misfolding and then it can travel up into the brain. But this is all still quite speculative, but certainly this is an area of research that we need to do more in.

Chris - And how does the appendix come into the picture?

Claire - This is a great question. As you've said already, there's really conflicting evidence so far as to whether people who have their appendix removed are more or less likely to get Parkinson's later. There's been studies that show people are more likely to, if they have their appendix removed and studies that show, they're less likely. There have also been studies more recently that show there's no difference in risk. So the picture is very mixed. One thing that I think is really interesting is that research has shown that in the appendix there does seem to be quite a lot of alpha-synuclein, this protein that I was speaking about, that we believe to be really at the heart of the problems in Parkinson's. So potentially the appendix could be the source of alpha-synuclein becoming misfolded and then travelling up through the nervous system into the brain, potentially. Of course, there's also this idea as well that's been discussed of the appendix being a safe haven for good bacteria. So we know that people with Parkinson's struggle to have the right bacteria in their gut. They have issues with constipation and things like this. So perhaps the appendix also has a protective role in Parkinson's in helping people to maintain good healthy microbiomes. So it might be that it has a dual role and it can have good and bad impacts for Parkinson's, and that's why we're seeing such different outcomes in some of the studies that have been done so far. But certainly it's part of this whole mystery we're trying to unravel in what role does the gut play in Parkinson's.