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The appendix has long been considered an organ having lost its usefulness in human evolution. But new research suggests that it could play an active – and detrimental – role in the development of Parkinson's disease.
In a discovery that extends the link between intestinal health and brain health in a surprising new direction, scientists found that people whose appendix had been removed were 20% less likely to develop neurodegenerative disease than people not presenting with appendectomy.
In addition, surgical removal of the appendix appeared to prevent Parkinson's symptoms, including tremors, movement difficulties, and signs of dementia. Of the older patients diagnosed with Parkinson's disease, those who had their appendix removed had their first symptoms 3.6 years later, on average, compared to those who had retained the tiny organ.
The authors of the new study, published Wednesday in the journal Science Translational Medicine, emphasized that their findings do not argue in favor of appendectomies as a strategy for the prevention of Parkinson's disease.
On the contrary, they say, the study offers new evidence for an idea that garners support from scientists exploring the origins of Parkinson's disease: at least in some cases, the proteins that accumulate in the brain and stop the production of dopamine are hatched gastrointestinal tract, possibly by the immune system.
From there, scientists suspect these proteins – called alpha-synuclein – to migrate northward along the vagus nerve, one of the body's longest nerves. In Parkinson's, these proteins are somehow "misfolded" and contribute to the formation of aggregates called Lewy bodies, which invade and damage a brain site that helps regulate movement.
Although far from definitive, this new picture of Parkinson's disease has begun to guide scientists to ways to detect and even treat this disease for years before it harms the brain. Gastrointestinal symptoms, such as chronic constipation, are often evident in people who have not been diagnosed with Parkinson's disease – a fact that has sparked interest in the link between the brain and the intestine in the disease and the possibilities of earlier detection.
But there are still many mysteries to solve. Scientists must define all the characters, including genes, environmental toxins and misfolded proteins, involved in the initiation and progression of the disease. They must discern where and how the disease process begins. And they must understand the exact sequence of events by which these multiple contributors interact to cause harm.
New discoveries suggest that the appendix should be a special place of interest for this hunt.
"It's a piece of the puzzle," said Dr. Rachel Dolhun, a neurologist and vice-president of medical communications at the Michael J. Fox Foundation, a major funder of Parkinson's research. "This suggests that the misfolding of proteins in the peripheral organs could be a factor in the onset of the disease, and that the appendix could be an organ likely to contribute."
Scientists observed for the first time two decades ago that abnormal alpha-synuclein proteins were evident in the brains of people with Parkinson's disease as a component of Lewy bodies. More recently, they discovered that, in their normal form, these alpha-synuclein proteins were widely distributed in the intestines of younger, healthy people.
Suspicions have increasingly weighed on the appendix as a breeding ground for potentially troublesome proteins. The appendix is a small-shaped protuberance of the large intestine. It is a common site of acute inflammation causing pain and inflammation in the intestines. Surgeons regularly remove it when it goes off.
But scientists have studied the varied ecosystem of microbes in the digestive tract and increasingly understood the role of the appendix in regulating immune responses in the gut – with repercussions on the entire body. If alpha-synuclein is created here or if the appendix generates the misfolded proteins that are the hallmark of Parkinson's disease, the presence or absence of an appendix should make all the difference so that the person can develop this disease, the authors of the new reasoned study.
It was a hypothesis that they could test if they managed to go through the complete medical records of a large population over many decades. In Sweden, a country with careful records and a national register of patients followed from cradle to grave, they had two options.
The first was a database containing detailed medical records for 1.6 million Swedes over an average of 54 years. Many of them had appendectomies; far fewer of them have been diagnosed with Parkinson's.
The analysis revealed that withdrawal of the appendix at the beginning of life was associated with a risk of developing Parkinson's disease reduced by about 20%.
The effect has been amplified in people living in rural areas. Environmental contaminants have been found to increase the risk of Parkinson's disease, and increased pesticide exposure in rural areas is generally thought to account for the greater prevalence of Parkinson's in this region. In this population, appendicectomies were associated with a 25% reduced Parkinson's risk.
When the researchers considered the timing for an appendectomy, they found further evidence suggesting a central role of the appendix in Parkinson's disease.
The decreased risk of Parkinson's only appeared when the appendix and the alpha-synuclein proteins it contains were eliminated early in life. The removal of the appendix after the beginning of the pathological process, however, did not have an effect on the progression of the disease, they discovered.
The study authors also analyzed appendix tissue samples from 48 individuals who had routine appendectomies and were not diagnosed with Parkinson's later in life. They found that 46 of the samples contained high levels of alpha-synuclein aggregates similar to those seen in Lewy bodies and that the age of the person from whom they had been excised did not seem to be of importance. In a disease related to advanced age, it was a surprise.
In the lab, researchers found that excised tissue from healthy individuals could easily form the dangerous lumps seen in the brains of people with Parkinson's disease.
All this suggests a model in which undesirable alpha-synuclein species could revive the formation of misfolded protein clusters inside the appendix, the authors wrote.
But that does not mean that the riddle of Parkinson's disease, first described in 1817 by Dr. James Parkinson, is about to be resolved. (Coincidentally, Parkinson was the first to describe acute appendicitis in 1812).
"There could be many origins" of the disease, said co-author Viviane Labrie, a neurogeneticist at the Van Andel Research Institute in Grand Rapids, Michigan. The removal of the appendix "seems to be associated with a 20% reduction in this risk." But, if this is a solid conclusion, it leaves a lot to explain.
(EDITORS: HISTORY CAN END HERE)
"This work is well done and the size of the population used by these authors is very powerful," said Anumantha Kanthasamy, a researcher on Parkinson's disease at Iowa State University in Ames, who did not participate in the study. new search.
Kanthasamy pointed out that the association found in the study did not necessarily suggest that withdrawal from the appendix directly reduced Parkinson's risk in Sweden. The relationship may well be more complex: for example, the appendicitis attack that led to the removal of the organ may ultimately be considered the key to protecting a person.
This adds to the concept that in Parkinson's disease, changes that occur in the peripheral nervous system, including in the intestine, probably occur much earlier than what you see as a classic pathology of the brain ", he added. "And that adds to our understanding that the intestine and the peripheral nervous system are intimately linked to the brain."
PHOTO (for help with images, contact 312-222-4194): SCI-PARKINSONS-APPENDIX
Copyright 2018 Tribune Content Agency.
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