COMMENTARY

Does Appendectomy Reduce the Chance of Developing Parkinson's?

F. Perry Wilson, MD, MSCE

Disclosures

November 06, 2018

Welcome to Impact Factor, your weekly dose of breaking medical research. I'm Perry Wilson.

This week, a study that made me say, "Wait, what?"

Source: Sci Transl Med. 2018;10:eaar5280. DOI: 10.1126/scitranslmed.aar5280

What does the appendix have to do with Parkinson's disease? Well, on its own, not very much. But in terms of our understanding of Parkinson's, quite a lot, actually.

The study, appearing in Science Translational Medicine, is really a series of studies, all focusing on a central hypothesis: that aggregated alpha-synuclein, the principal component of Lewy bodies (which are themselves a pathognomonic finding in Parkinson's disease), may originate not from the brain but from the gut.

Source: Wikimedia Commons

Is this plausible?

Actually, it is. Studies have shown that infection and toxins can promote aggregation of alpha-synuclein in neurons in the GI tract. Furthermore, this aggregated alpha-synuclein may promote further aggregation of alpha-synuclein in a prion-like fashion. In fact, the aggregated alpha-synuclein may travel right up the vagus nerve from the gut to the brain and start a cascade of reactions that ultimately may lead to Parkinson's disease.

Source: Wikimedia Commons

OK, you heard a lot of "mays" there; this is all really hypothetical stuff—not concrete.

What does this have to do with the appendix? Well, we continue to learn that the appendix may not be a purely vestigial organ and may play a significant role in immune surveillance and reconstitution in the GI tract.

Oh, and when you section a healthy appendix and stain it for alpha-synuclein, this is what you get. The alpha-synuclein is in red here. Yup—it's all over the place.

Source: Sci Transl Med. 2018;10:eaar5280. DOI: 10.1126/scitranslmed.aar5280

The authors of the Science Translational Medicine study actually looked at appendixes from individuals with Parkinson's disease and healthy controls. They both contained similar amounts of alpha-synuclein, but the alpha-synuclein was more insoluble in the patients with Parkinson's—just like the alpha-synuclein seen in brain biopsies.

Source: Sci Transl Med. 2018;10:eaar5280. DOI: 10.1126/scitranslmed.aar5280

If you remove the appendix, you might get rid of some of that alpha-synuclein, right? Would the effect be noticeable?

So, due to universal healthcare stuff, Sweden has health records on all of its citizens, going back to the mid-1960s.

Source: Wikimedia Commons

The authors examined this data and found about half a million individuals who had an appendectomy. They matched them based on age, sex, and a few other factors to around 1.1 million people who didn't [have an appendectomy]. Then they looked forward in time to see who developed Parkinson's disease.

The results were subtle but highly statistically significant: 1.17 out of every 1000 people who had an appendectomy developed Parkinson's disease compared with 1.4 out of every 1000 people who didn't have an appendectomy—a nearly 20% reduction.

Source: Sci Transl Med. 2018;10:eaar5280. DOI: 10.1126/scitranslmed.aar5280

OK, let's pause. No, you should not have your appendix out. Although a 20% reduction sounds great, the absolute risk is so low as to make that number mostly meaningless. On the basis of these numbers, you'd need to remove 4347 appendixes to prevent one case of Parkinson's disease. Not the best prevention strategy, in my opinion.

But this study isn't really about appendectomies. This study is about adding weight to a controversial hypothesis that the origins of a devastating brain disease may lie not in the skull but in the gut. And that is certainly something to digest.

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