A large-scale epidemiological study has suggested that people who have their appendix removed at an early point in their life may display a reduced risk in developing Parkinson's disease. The compelling research found the appendix can hold a major volume of the toxic proteins that contribute to the progression of Parkinson's, adding weight to the hypothesis that this devastating neurodegenerative disease may originate outside of the brain.

The study utilized an enormous dataset of nearly 1.7 million people, with more than 500,000 having had an appendectomy at some point in their life. Overall, the results showed that subjects with no appendix were over 19 percent less likely to develop Parkinson's disease, and if they ultimately did develop the disease their diagnosis was an average of 3.6 years later than subjects with an appendix.

Interestingly, this effect was seen as even more powerful in people living in rural areas, who displayed a 25 percent reduced risk in developing Parkinson's following an appendectomy. Parkinson's disease is known occur at higher rates in rural areas, adding fuel to the hypothesis there is some unknown environmental trigger to the disease that is more prevalent in non-urban environments.

What makes this particular research a little more weighty than the usual observational study is the follow-up work conducted by the scientists, which explores a potential causal reason why the appendix may contribute to a heightened Parkinson's risk.

The primary pathological characteristic of Parkinson's disease is the progressive cell death of the brain's dopamine secreting neurons. Recent research has revealed the presence of toxic protein aggregates, called Lewy bodies, may be behind the neurodegeneration associated with the disease. Lewy bodies are spherical clumps of the protein alpha-synuclein.

The second part of this new study involved examining appendix tissue from 48 healthy individuals of varying ages, all without Parkinson's disease. All of these samples revealed the presence of alpha-synuclein in the appendix, regardless of the age of the subjects. The form of the alpha-synuclein found in the appendix tissue was remarkably similar to what is seen in the brains of Parkinson's patients.

"We were surprised that pathogenic forms of alpha-synuclein were so pervasive in the appendixes of people both with and without Parkinson's," explains senior author on the new study, Viviane Labrie. "It appears that these aggregates — although toxic when in the brain — are quite normal when in the appendix. This clearly suggests their presence alone cannot be the cause of the disease."

Of course this research raises an extraordinary number of questions that, at this point, cannot be easily explained. The scientists are clear in noting that this possible reservoir of alpha-synuclein in the appendix is not by any means the sole cause of Parkinson's disease. In fact, the key mystery raised by this research is more about how that particular protein could accumulate and then spread from the appendix to the brain.

"Parkinson's is relatively rare — less than 1 percent of the population — so there has to be some other mechanism or confluence of events that allows the appendix to affect Parkinson's risk," says Labrie. "That's what we plan to look at next; which factor or factors tip the scale in favor of Parkinson's?"

The research makes an important contribution to the growing body of work pointing to the significance of the gut-brain connection. No one is suggesting that we all run out and have our appendix removed to lower our Parkinson's disease risk, however this research does direct scientists toward new ways that could help us battle a variety of neurodegenerative disorders.

The study was published in the journal Science Translational Medicine.