Two new epidemiological studies have suggested an important role for the annex in connection with Parkinson's disease. A large study…
Two new epidemiological studies have suggested an important role for the annex in connection with Parkinson’s disease.
A large study involving the whole of Sweden’s population and having a 50-year follow-up found that people whose attachment had been removed in the early life had a 20% lower risk of developing Parkinson’s disease later in life.
The second study, from the United States, found that for patients with Parkinson’s disease whose attachment had been removed earlier in life, the age of disease outbreak was later than for those who had not undergone appendectomy.
Both studies were published online on October 31 in an article in Science Translational Medicine .
“Overall, our research shows the annex to be a tissue site that plays a key role in the initiation of Parkinson’s disease and also increases the interest in the potential of gastrointestinal-based therapies for treatment and prevention of Parkinson’s disease.” Senior Researcher Viviane Labrie, PhD, Van Andel Research Institute, Grand Rapids, Michigan.
Labrie spoke at a press conference organized by the American Association for the Advancement of Science, publisher of Science Translational Medicine. The news conference presented several authors of the article, ranging from Van Andel’s research institute.
The researchers also found a high level of alpha-synuclein clumps in adjuvant, both from patients with Parkinson’s and healthy subjects. Alfa-synuclein is known to be a factor in the pathology of Parkinson’s disease in the brain.
“We do not suggest removing the annex as a preventive treatment of Parkinson’s and we do not say that if you have had an appendectomy, you will not get Parkinson’s,” Labrie said. “But what we can say is that the attachment is a potential reservoir for the clumsy form of alpha synuclein associated with Parkinson’s disease in the brain. Although this clumsy alpha synuclein appears to be normal in the annex, it is pathogenic in the brain, so is the place all.
“These alpha synuclein clumps are found in the appendix of almost everyone, but we think that Parkinson’s patients fly these lumps through the vagal to the brain,” she said. inflammation of the gastrointestinal tract involving the attachment can play one role she added.
“Our results indicate that the annex is a potential starting point for Parkinson’s disease. But deletion of the annex does not completely eliminate the disease, so there are likely to be other important places of origin, says Labrie. “Instead of advocating universal appendctomy, it would be better to try to control the excessive formation of alpha synuclein clumps in the GI channel altogether and try to prevent their escape from the GI system to the brain.”
Labrie explained that Parkinson’s disease has been considered a disorder caused by loss of dopaminergic neurons in the brain’s substantia nigra. But over the past decade it has become apparent that the disease is not only a motor disorder but also includes a variety of non-motor symptoms, including symptoms that often occur in the years or even decades before engine symptoms develop.
“More clinical attention now focuses on the GI channel, not only in terms of symptoms but also as a possible place where Parkinson’s disease can commit n,” she added.
Parkinson’s disease is the appearance of Lewy bodies ̵
1; alpha synuclein lumps – in the brain. There is evidence that patients with Parkinson’s disease are also clumps of alpha synuclein present in the GI channel, sometimes many years before the onset of motor symptoms, Labrie noted.
“It also seems that alpha synuclein does not like to stay,” she said. “It can move from neuron to neuron and can stir nerves that connect the intestines in the brain where it causes neurotoxic effects. One of the first areas in the brain where these lumps of alpha synuclein are seen in Parkinson’s patients is the terminal on the vagalus, which connects the intestines in the brain, and the disease progresses and proceeds from there. “
Labrie said that her and her colleagues wanted to study specific areas of intestines that may be involved in Parkinson’s and focus on attachment, as the Annex plays an immunomodulatory role in the body.
“It is the responsibility for sampling and modulation of pathogens and raising an immune response,” she noted. “In addition, the intestinal microbiomy has been linked to Parkinson’s disease and the addition is a storage area for intestinal bacteria and can affect the regulation of bacteria in the GI area. Therefore, we conducted the current studies that investigate the effects of removing the Annex on Parkinson’s disease risk.”
The researchers first analyzed data from the Swedish Patient Register, which document hospitals and operations for the entire Swedish population.
The identified all individuals in Sweden who had their attachment were removed since 1964. Each of these patients was matched with two control subjects from the general population who had not undergone appendectomy. The researchers analyzed data from a total of 1.7 million individuals. Monitoring data was available for up to 52 years.
The results showed that the risk of developing Parkinson’s disease was reduced by almost 20% among people who had removed their attachment.
The incidence of Parkinson’s disease was 1.60 per 100,000 years of age among subjects who had undergone appenditomy versus 1.98 for control subjects, which meant a risk reduction of 19.3% (95% confidence interval, 10.4% – 27 , 2%).
The risk reduction was even greater (around 25%) in people living in rural areas, which indicates that environmental factors may also be involved.
In the Swedish study among those who developed Parkinson’s disease, the age of diagnosis was on average 1.6 years later in people who had undergone an appendctomy 20 or more years earlier than those who had not undergone an appendctomy.
From the second data set – the US Parkinson’s Progression Markers Initiative – the researchers analyzed data on 849 patients with Parkinson’s disease and found that 6.5% had undergone appendectomy earlier in life.
For those who had undergone an appendectomy, the age of Parkinson’s disease was 3.6 years later on average than in those patients
The researchers reviewed appendices from 48 healthy individuals and found a “remarkable abundance” of the clumsy form of alpha -synuclein in 46 of 48 samples.
“This is important, as before, we thought that these lumps of alpha synuclein would only occur in Parkinson’s patients. However, our findings show that in the appendix they are as rich in healthy individuals,” says Patrik Brundin, MD. Levels were also similar to normal and acute and chronically inflamed additive tissue and in younger and older.
“It appears that the presence of alpha synuclein aggregates in the car’s nerve cells is not a feature unique to Parkinson’s disease, as it is found in almost all individuals. It is also not associated with aging,” added Brundin.
However, with further biochemical analysis, researchers found that some forms of alpha synuclein were more common in the annex to Parkinson’s patients. In particular, there was a 4.5-fold increase in truncated alpha synuclein, which is prone to extremely fast lumping, said the main author of the article, Bryan Killinger, PhD.
“Our data indicate that there is a unique abbreviation of alpha synuclein in the appendix, which accelerates the ability to form clumps and is a risk factor for Parkinson’s disease,” he concluded. “Future research could focus on this truncated form of the protein.”
As a commentary to the study, Orla Smith, MD, editor of Science Translational Medicine said: “This document provides clear evidence that pathogenic events take place in the GI system and the enteral nervous system.
“The authors show that the human attachment may be a reservoir for pathogenic forms of alpha synuclein known to cause Parkinson’s disease when mutated in the brain,” she said. Science Translational Medicine is excited to publish this carefully completed study that extends our understanding of the earliest stages of one of the most common and debilitating neurological diseases. “
Sci Transl Med. Published online on October 31. Full text
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