Appendectomy Linked to Lower Rates of Parkinson's Disease. Wait, What?

The new study found a small, but significantly lower rate of Parkinson’s disease among those who had appendectomies compared to those who hadn’t.

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 α-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.

Is this plausible?

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

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 α-synuclein this is what you get.  The α-synuclein is in red here.  Yup.  It’s all over the place.

 Red = α-synuclein. Blue = nuclei mostly

Red = α-synuclein. Blue = nuclei mostly

 The appendixes of individuals with Parkinson’s disease have higher insoluble α-synuclein content.

The appendixes of individuals with Parkinson’s disease have higher insoluble α-synuclein content.

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

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

So, due to universal health care stuff, Sweden has health records on all of its citizens going back to the mid 60’s.

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

 Yeah but check out that Y-axis…

Yeah but check out that Y-axis…

The results were subtle, but highly statistically significant.

1.17 out of every 1000 people who had an appendectomy developed Parkinsons’ disease compared to 1.4 out of every 1000 people who didn’t have an appendectomy – a nearly 20% reduction.

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. Based on 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.

This commentary first appeared on Medscape.com.