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The appendix could be a starting point for Parkinson’s

A large research study shows that the appendix acts as a reservoir for disease-associated proteins and appendectomy lowers the risk of developing Parkinson’s disease.

The study involved scientists from Van Andel Research Institute, Northwestern University, Lund University and Michigan State University, and the results was published recently in Science Translational Medicine. 

And according to the new study, removing the appendix early in life reduces the risk of developing Parkinson’s disease by 19 to 25 percent. The findings also solidify the role of the gut and immune system in the genesis of the disease, and reveal that the appendix acts as a major reservoir for abnormally folded alpha-synuclein proteins, which are closely linked to Parkinson’s onset and progression.

The reduced risk for Parkinson’s was only apparent when the appendix and the alpha-synuclein contained within it were removed early in life, years before the onset of Parkinson’s, suggesting that the appendix may be involved in disease initiation. Removal of the appendix after the disease process starts, however, had no effect on disease progression.

In a general population, people who had an appendectomy were 19 percent less likely to develop Parkinson’s. This effect was magnified in people who live in rural areas, with appendectomies resulting in a 25 percent reduction in disease risk. Parkinson’s often is more prevalent in rural populations, a trend that has been associated with increased exposure to pesticides.

Appendectomy can delay disease progression

The study also demonstrated that appendectomy can delay disease progression in people who go on to develop Parkinson’s, pushing back diagnosis by an average of 3.6 years. Because there are no definitive tests for Parkinson’s, people often are diagnosed after motor symptoms such as tremor or rigidity arise. By then, the disease typically is quite advanced, with significant damage to the area of the brain that regulates voluntary movement.

Conversely, appendectomies had no apparent benefit in people whose disease was linked to genetic mutations passed down through their families, a group that comprises fewer than 10 percent of cases.

The team also found clumps of alpha-synuclein in the appendixes of healthy people of all ages as well as people with Parkinson’s, raising new questions about the mechanisms that give rise to the disease and propel its progression. Clumped alpha-synuclein is considered to be a key hallmark of Parkinson’s; previously, it was thought to only be present in people with the disease.

Data from the Swedish National Patient Registry

Data for the study were gleaned from an in-depth characterization and visualization of alpha-synuclein forms in the appendix, which bore a remarkable resemblance to those found in the Parkinson’s disease brain, as well as analyses of two large health-record databases.

The first dataset was garnered from the Swedish National Patient Registry, a one-of-a-kind database that contains de-identified medical diagnoses and surgical histories for the Swedish population beginning in 1964, and Statistics Sweden, a Swedish governmental agency responsible for official national statistics. The team at VARI collaborated with researchers at Lund University, Sweden, to comb through records for 1,698,000 people followed up to 52 years, a total of nearly 92 million person-years.

The second dataset was from the Parkinson’s Progression Marker Initiative (PPMI), which includes details about patient diagnosis, age of onset, demographics and genetic information.

Image caption: The hallmark pathology of Parkinson’s disease is detected in the healthy human appendix. Clumped forms of alpha-synuclein proteins are a key feature of Parkinson disease, but new research shows that nerve cells of the human appendix also hosts an abundance of clumped alpha-synuclein. Appendix nerve cells are colored in green, clumped alpha-synuclein is colored in red, and nuclei of appendix nerve cells are colored in blue. This suggests that clumped alpha-synuclein is normally present in the appendix but if it were to leave and enter the brain it could trigger Parkinson’s disease. Copyright: Van Andel Institute

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