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In science, the mantra "correlation does not cause causation" is a cornerstone of proper data analysis and hypothesis training. Yet, for researchers, this code is not a stopping point, but often has a springboard to dive more deeply into the data and discover the mechanisms that led to the curious findings. When the data is supported by a population of almost 2 million, it is probably a statistical artifact. This is the most important case for an international research team by the Van Andel Research Institute (VARI), which suggests that removing the appendix early in life reduces the risk of developing Parkinson's disease by 19 to 25 percent.
The findings from this study are published late in the year Science Translational Medicine This article is published in the English version of the English version of the English version of the '' '' '' '' '' '' '' '' '' '' '' '' '' '' '' '' '' '' '' proteins, which are closely linked to Parkinson's onset and progression.
"Our results point to the appendix as a site of origin for Parkinson's and provide a pathway forward for new treatment strategies that leverage the gastrointestinal tract's role in the development of the disease," explained senior study investigator Viviane Labrie, Ph.D. an assistant professor VARI. "Despite having a reputation as necessary, the appendix actually plays a major role in our immune systems, in regulating the makeup of our gut bacteria, as shown by our work, in Parkinson's disease."
Interestingly, 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 has been achieved in rural areas, with appendectomies resulting in a 25 percent reduction in disease risk. Parkinson's is often more prevalent in rural populations, which is associated with increased exposure to pesticides.
"We determined the capacity of the appendix to modify PD risk and influence pathogenesis," the authors wrote. "In two independent epidemiological datasets, involving more than 1.6 million individuals and over 91 million person-years, we observed that removal of the appendix decades before PD onset was associated with a lower risk for PD, particularly for individuals living in rural areas, and delayed the age of PD onset. "
The research team also found 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, they are often diagnosed after these symptoms. 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 their genetic mutations, which was less than 10 percent of cases.
Bryan Killinger, Ph.D., is a postdoctoral fellow in Dr. Labrie's laboratory. "We have shown that the appendix is a hub for the accumulation of clones of alpha-synuclein proteins, which are implicated in Parkinson's disease." This knowledge will be invaluable as we explore new prevention and treatment strategies.
Amazingly, the researchers also found clocks of alpha-synuclein in the appendixes of healthy people with Parkinson's, raising new issues about the mechanisms that give rise to disease and propel its progression. Clumped alpha-synuclein is considered to be a hallmark of Parkinson's-previously, it was thought to be present in people with the disease.
"We also found that the healthy human appendix contained intraneuronal α-synuclein aggregates and an abundance of PD pathology-associated α-synuclein truncation products that are known to accumulate in human organs, the pathological hallmark of PD," the authors penned. "Lysates of human appendix tissue-induced rapid cleavage and oligomerization of full-length recombinant α-synuclein."
Data for the study has been published in the field of alpha-synuclein forms in the appendix, which has a remarkable resemblance to those found in the Parkinson's disease brain, as well as analyzes of two large health-record databases. The first dataset was of 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. The team at VARI is collaborating with researchers at Lund University, Sweden, with a combined record of 1,698,000 people, followed by a total of nearly 92 million person-years. The second dataset was from the Parkinson's Progression Marker Initiative, which includes details about patient diagnosis, age of onset, demographics, and genetic information.
"We were surprised that these pathogenic forms of alpha-synuclein were so pervasive in the appendixes of both people with Parkinson's." It appears that these aggregates are toxic when in the brain-are quite normal when in the appendix. presence alone can not be the cause of the disease, "Dr. Labrie concluded. "Parkinson's is relatively rare-1% of the population-so there is a difference in the incidence of Parkinson's risk. in favor of Parkinson's? "
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