Appendectomy May Reduce Parkinson's Disease Risk

A new study suggests that the normal human appendix contains pathogenic forms of α-synuclein, which affect the risk of developing Parkinson's disease (PD).

Researchers at the Van Andel Research Institute (VARI; Grand Rapids, MI, USA), the Centre for Addiction and Mental Health (CAMH; Toronto, Canada), and other institutions conducted two independent epidemiological studies that analyzed datasets from the Swedish National Patient Registry in order to determine the capacity of the appendix to modify PD risk and influence pathogenesis. The study included 1,698,000 individuals followed for up to 52 years, for a total of nearly 92 million person-years.

The results showed that the risk of developing PD was 19% lower among those who had their appendix surgically removed in childhood. Further analysis suggested people who developed PD despite an early-in-life appendectomy tended to have symptoms appear 3.6 years later than similarly aged patients, and that people living in rural areas benefited most. The researchers then examined appendix tissue from 48 healthy people; in 46 of them, they found intraneuronal α-synuclein aggregates and an abundance of α-synuclein truncation products known to accumulate in Lewy bodies, the pathological hallmark of PD.

They also found that the healthy human veriform appendix contained Lysates of human appendix tissue that induced rapid cleavage and oligomerization of full-length recombinant α-synuclein. They therefore propose that the normal human appendix inherently contains pathogenic forms of α-synuclein that can affect the risk of developing PD, and that whether the appendix was inflamed or not was negligible. The study was published on October 31, 2018, in Science Translational Medicine.

“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 senior author Viviane Labrie, PhD, of VARI. “Despite having a reputation as largely unnecessary, the appendix actually plays a major part in our immune systems, in regulating the makeup of our gut bacteria and now, as shown by our work, in Parkinson’s disease.”

“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,” concluded Dr. Labrie. “Parkinson’s is relatively rare, less than one 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.”

The appendix is a narrow, elongated, blind-ended extension of the large intestine that projects from the cecum, near the juncture with the small intestine. More correctly known as veriform appendix due to its worm-like hollow shape, the appendix is present only in humans, certain anthropoid apes, and the Australian wombat. The appendix is rather well known despite its small size and obscure location, both because of its propensity to be easily infected by bacteria, leading to appendicitis, and because it’s function remains unclear.

Related Links:
Van Andel Research Institute
Centre for Addiction and Mental Health