By Marilynn Larkin
NEW YORK (Reuters Health) - Removal of the appendix is linked with lower Parkinson's disease (PD) risk, particularly for people in rural regions, and this finding may shed light on the etiology of the disease, researchers say.
Dr. Viviane Labrie of the Van Andel Research Institute in Grand Rapids, Michigan told Reuters Health, "Our research identified the appendix as a potential starting point for PD, which was both surprising and exciting."
"One of the most significant findings was an abundance of the clumped protein, alpha-synuclein, in the appendixes of all people of all ages," she said by email. "Previously, these clumps were thought to only be present in people with Parkinson's. This tells us that the clumps themselves are not a defining feature of the disease; there must be another trigger mechanism or mechanisms needed to tip the scale toward Parkinson's."
"Importantly, we are not suggesting that people should undergo appendectomies as a way to reduce risk," Dr. Labrie said. "Instead, we think this is an important avenue for better understanding the disease and finding new ways to manage these problematic proteins before they kick-start the disease process."
Dr. Labrie and colleagues studied more than 1.6 million people in Sweden, including 849 individuals with Parkinson's disease.
As reported online October 31 in Science Translational Medicine, appendectomy was associated with an overall PD risk reduction of 19.3%. Specifically, PD incidence was 1.60 per 100,000 person-years among individuals who had an appendectomy compared to 1.98 for controls.
Further, the cumulative prevalence of PD in people who had an appendectomy was also lower by 16.9% relative to the general population: PD was diagnosed in 1.17 out of every 1,000 people who had an appendectomy compared to 1.4 per 1,000 in the general population.
The effect of appendectomy was greatest among rural residents. Those with an appendectomy had a significant 25.4% decrease in PD risk; no such benefit of appendectomy was seen for people living in urban areas. Further, an appendectomy 20 years prior to diagnosis was also associated with a significant delay in the age of PD diagnosis in rural, but not urban, residents.
"These findings suggest that appendectomy influences environmental risk factors for PD, specifically for individuals living in rural environments," the authors state.
The team also found the age of PD diagnosis was, on average, 3.6 years later in individuals who had an appendectomy occurring at least 30 years before disease onset relative to those without an appendectomy.
As Dr. Labrie noted, additional investigations showed that the healthy human appendix contains intraneural alpha-synucelin aggregates and PD pathology-associated substances that may affect the risk of developing PD.
"Rather than surgery," she added, "a better way to leverage these findings might be to control the levels of alpha-synuclein in the gut, before it gets to the brain. There are several drugs currently in clinical trials that may aid in this effort."
Dr. Michael Okun, Medical Director of the Parkinson's Foundation, told Reuters Health by email, "Several recent studies contradict some of the findings. These studies collectively have indicated no change or only a slight change in Parkinson's disease risk following appendectomy."
"Collective wisdom in medicine when proving an association is best achieved when multiple well designed studies can replicate a finding," he added. "Based on what we currently know, alpha-synuclein can definitely be present in the appendix."
Like Dr. Labrie, Dr. Okun said, "We do not recommend surgical appendectomy to prevent or delay Parkinson's disease in at risk groups (those with genetic risk factors or family histories)."
Sci Transl Med 2018.
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