The relationship between the appendix and Parkinson’s disease

The relationship between the appendix and Parkinson’s disease

Two recent publications probed the relationship between the human appendix and the development of Parkinson’s disease (PD). One of the articles, published in September 2018 in the journal Movement Disorders examined whether a history of an appendectomy affected the risk of developing PD. Using two large datasets of health information gathered from healthy volunteers over decades (one containing about 275,000 people and the other containing about 50,000 people), the data demonstrated that there was no change in risk of PD depending of whether a person had a prior appendectomy. This study’s results are the same as three previous studies, each analyzing its own large dataset.

More recently, an article appearing in the journal Science Translational Medicine, came to a different conclusion – that the appendix may indeed play a role in the development of PD. This study also used two databases, one large administrative database of health information from 1.9 million people in Sweden and also the data collected from well characterized patients with PD, as part of the Parkinson’s Progressive Marker Initiative (PPMI). The data from these studies showed an approximately 20% decline in the rates of PD in those who had an appendectomy, even decades earlier. It also showed that in those who did develop PD, the age of onset was on average 3.6 years later in someone who had an appendectomy as compared to someone who did not. The study further demonstrated that alpha-synuclein aggregates, the pathologic hallmark of PD, exist in the neurons that line the appendix, even in people without PD, suggesting that the appendix may be a source of abnormal alpha-synuclein, triggering PD in a subset of people. It is well known that gastro-intestinal symptoms are often prominent in people with PD, sometimes decades before motor symptoms and alpha-synuclein aggregates are found throughout the GI tract in people with PD (see a recent blog post which discusses these issues).

How are we to explain the differences in results between these two papers? The newest journal article suggests that that study used a database that was significantly larger and had the longest follow up of any of the databases analyzed previously, so that may have played a role in the outcome No one, however, not even the authors of the paper which demonstrated that appendectomy lowered PD risk, would suggest that a person should undergo an appendectomy in order to lower their PD risk.

Interestingly, this second study received much attention in the mainstream media, whereas the paper which did not show a relationship between appendectomy and PD (as well as the three prior studies with that same result), was not covered. What these contradictory papers demonstrate is that scientific results must be interpreted carefully and with an understanding of all the available research, and that results that seem exciting are much more likely to appear in the mainstream media than results that are less exciting. Further investigation of the relationship between the appendix and PD is necessary, which may help us gain a deeper understanding of how PD develops.

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