Neurology Central

Could the appendix be a starting point for Parkinson’s disease?

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Researchers have identified the appendix as a reservoir for disease-associated proteins related to Parkinson’s disease (PD), with appendectomy shown to lower the risk of PD development in the largest epidemiological dataset study yet.

Viviane Labrie, research lead from Van Andel Research Institute (MI, USA) and her team studied two independent epidemiological datasets involving 1.6 million individuals, and observed that removal of the appendix decades before PD onset reduced the risk of developing PD by between 19 to 25%.

The study examined the health records of 1,698,000 individuals with and without previous appendectomy, using data from the Swedish National Patient Registry and Statistics Sweden. The researchers de-identified medical records and surgical histories for the Swedish population and people with PD were then identified in the follow-up.

The results of the study implied the role of the appendix and the immune system as a site of origin of the disease, as the appendix was found to contain intraneuronal α-synuclein truncation products, which are closely linked to the progression and onset of PD.

The reduced risk for PD was made apparent when the appendix and the α-synuclein contained within it were removed early in life, which suggested that the appendix could be involved in disease initiation.

“Our results point to the appendix as a site of origin for Parkinson’s and provide a path forward for devising new treatment strategies that leverage the gastrointestinal tract’s role in the development of the disease,” said Labrie.

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The study demonstrated that in individuals who had undergone an appendectomy, the overall risk for PD, as well as the age of onset, was affected. In a general population, people were 19% less likely to develop PD if they had previously undergone appendectomy. The effect was magnified to a 25% reduction in disease risk for people who lived in rural areas.

Appendectomy was also found to push back disease progression in people who go on to develop PD, delaying onset by an average of 3.6 years. For individuals whose disease was linked to genetic mutations, appendectomies had no apparent benefit.

The team also found clumps of α-synuclein in the appendixes of healthy people as well as those with PD, which raised questions about the pathological mechanisms and progression of PD, as clumped α-synuclein is considered to be a key contributor to the disease.

“Our findings today add a new layer to our understanding of this incredibly complex disease,” explained Bryan Killinger, the study’s first author and a postdoctoral fellow in Labrie’s laboratory. “We have shown that the appendix is a hub for the accumulation of clumped forms of α-synuclein proteins, which are implicated in PD. This knowledge will be invaluable as we explore new prevention and treatment strategies.”

“We were surprised that pathogenic forms of α-synuclein were so pervasive in the appendixes of people both with and without Parkinson’s. 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,” commented Labrie.

Labrie believes that “there has to be some other mechanism or confluence of events that allows the appendix to affect Parkinson’s risk” and in future plans to look at what factors tip the scale in favor of PD.

Sources: Killinger BA, Madaj Z, Sikora JW et al. The vermiform appendix impacts the risk of developing Parkinson’s disease. Sci. Transl. Med. 10, eaar5280 (2018) (Epub ahead of print); Van Andel Research Institute. Appendix identified as a potential starting point for Parkinson’s disease. Press release: www.vai.org/news-release-10-31-2018/

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