Although its exact role isn’t yet clear because findings have been conflicting, in this easy-to-read overview the link between the appendix in the gut and risk of developing Parkinson’s is discussed.

This easy-to-read overview was published in the journal JAMA on the link between the appendix and the risk of developing Parkinson’s. A special mention is given to research conducted by Prof Patrik Brundin (Chair iLCT committee) and colleagues at Van Andel Institute (VAI) in Grand Rapids.

Unless it becomes inflamed, most people don’t give the appendix a second thought. But recent studies suggest that the rather unremarkable organ plays a role in determining whether its owner will someday be diagnosed with Parkinson’s. The appendix’ role isn’t yet clear because findings have been conflicting. One study linked removal of the appendix to a lower risk of Parkinson’s, while the other linked removal to a higher risk!

However, both studies implicate the protein alpha-synuclein, large aggregates of which form Lewy bodies – abnormal deposits in dopamine-producing neurons in the brains of people with Parkinson’s. While Lewy bodies are a hallmark of Parkinson’s, whether they cause the disease is not yet clear.

Studies suggest normal alpha-synuclein is involved in neurotransmission. The protein is also found in the gastrointestinal tract, which is why scientists have looked for a connection between the appendix and Parkinson’s.

In one study researchers analysed electronic health records from more than 62.2 million US patients and identified 488,190 who had undergone appendectomies. Of those, 0.92%, were diagnosed with Parkinson’s at least six months after their appendectomy. Of those who had not undergone an appendectomy, only 0.29%, were diagnosed with Parkinson’s. In other words, those who no longer had their appendix were more than three times as likely to develop Parkinson’s than those who still had theirs. The increased risk in people who’d had an appendectomy occurred in all age groups, regardless of sex or race.

There are a number of speculations of why the risk increased (although this risk is still small). An appendectomy for example could increase risk because during the operation, αlpha-synuclein might be spread to the brain by way of the vagus nerve, or, perhaps, it’s not the appendectomy itself at play but rather the inflammation from appendicitis. 

Another explanation could be the reason that the appendix is removed – because the appendix is considered a vestigial organ it is often removed when operations for other conditions like hysterectomies or ovaryectomies are carried out – ‘We’re in there anyway, let’s just remove it’.

Other statistical information such as those who smoked or those who took anti-inflammatory drugs were not accounted for in the study and these potential ‘confounders’ have actually been linked to a lower risk of Parkinson’s.

In another study, scientists analysed two data sets involving more than 1.6 million people, virtually all of whom lived in Sweden, and more than 91 million person-years over more than a half-century of follow-up. The researchers found that the incidence of Parkinson’s among those who’d undergone an appendectomy was 1.6 per 100 000 person-years, compared with 1.98 per 100 000 among those who had not. Among people with Parkinson’s, those who’d had an appendectomy were diagnosed on average 3.6 years later in age than those who had not had an appendectomy.

Unlike the former study, this study knew how much time had elapsed between an appendectomy and diagnosis, which could help explain why their findings were so different, said Viviane Labrie, PhD, study co-author and an assistant professor in the Center for Neurodegenerative Science at VAI.

The former study authors (Cooper et al.) acknowledged this limitation, noting they could not determine how much time beyond six months had elapsed between appendectomy and a Parkinson’s diagnosis. In other words, people might already have started down the path to Parkinson’s when they underwent the appendectomy, so the association between the procedure and their diagnosis might have been spurious.

It was noted that determining a trigger for Parkinson’s should be examined at least 20 years earlier than the diagnosis, since the time the hallmark movement problems appear, leading to a Parkinson’s diagnosis, more than half of the cells in the substantia nigra have been destroyed.

An unusual component of Labrie’s research work was the examination of appendixes removed from 48 individuals who did not have Parkinson’s. The researchers found “abundant” pre-Lewy body aggregates of alpha-synuclein in 46 of the 48 appendixes, which had been removed from patients ranging in age from infancy to 84 years. We didn’t expect to see clumped proteins in healthy individuals, Labrie said, adding that the finding suggests the aggregates have an as-yet undetermined normal biological function in the appendix.

Other studies suggest that alpha-synuclein aggregations might start in the enteric nervous system (that which governs the function of the gastro-intestinal system) and the olfactory bulb and then travel to the brain via the vagus nerve and the olfactory tract.

In conclusion, and based on these findings, should people consider having their appendix removed even if they don’t have appendicitis? Labrie suggests not. In the end, the clumped protein could exist in other parts of the GI tract that haven’t been looked at yet.

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