The appendix has long been dismissed as an organ that has survived its usefulness for human evolution. New research indicates, however, that it may play an active – and detrimental – role in the development of Parkinson's disease.

In a finding that expands the link between gut and brain health in a startling new direction, scientists found that people who had the appendix removed were 20 percent less likely to develop a neurodegenerative disease than people who had had no ankleectomy.

In addition, surgical removal of the cecum appeared to prevent the onset of Parkinson's symptoms, including tremors, movement disorders, and signs of dementia. In elderly patients who were eventually diagnosed with Parkinson's disease, those who had their appendix removed their first symptoms on average 3.6 years later than 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 did not suggest appendectomies as a strategy to prevent Parkinson's disease.

Rather, the study provides new evidence for an idea that finds support among scientists who explore the origins of Parkinson's Disease: that, at least in some cases, the proteins that accumulate in the brain and shut down dopamine production are hatched in the brain Gastrointestinal tract, possibly through the immune system.

From there, scientists suspect that these proteins – called alpha synuclein – travel north along the vagus nerve, one of the longest nerves in the body. In Parkinson's, these proteins are somehow "misfolded" and contribute to the formation of lumps, the so-called Lewy bodies, which invade and damage a site in the brain that contributes to the regulation of movement.

While this is far from final, this emerging picture of Parkinson's disease has begun to focus scientists on how they might recognize and even treat it for years before it is damaged in the brain. Gastrointestinal symptoms, such as chronic constipation, often occur in people who have diagnosed Parkinson's disease – a fact that has sparked interest in the brain-bowel connection to the disease and the potential for early discovery.

However, there are still many puzzles to solve. Scientists need to capture the full range of characters – including genes, environmental toxins and misfolded proteins – that are involved in the onset and progression of the disease. They must recognize where and how the disease process begins. And they need to understand the exact order of events through which these multiple contributors interact to cause harm.

The new findings suggest that the appendix should be a special attraction in this hunt.

"It's part of the puzzle," Dr. Rachel Dolhun, neurologist and vice president of medical communications at the Michael J. Fox Foundation, a major contributor to Parkinson's research. "It is thought that the misfolding of proteins that can occur in peripheral organs is a causative factor for the disease and that the attachment could be an organ that could help."

For the first time two decades ago, scientists have observed that abnormal alpha-synuclein proteins are found in the brains of Parkinson's patients as part of Lewy bodies. Recently, they have discovered that these alpha-synuclein proteins in their normal form are widely distributed in the gut of healthy young people.

Suspicions increasingly came on the attachment as a breeding ground for the potentially annoying proteins. The cecum is a slender, colon-shaped elevation of the colon, a common site of acute inflammation that causes pain and inflammation throughout the intestine. Surgeons remove it regularly when it flares.

However, as scientists have studied the diverse microbial ecosystem in the digestive tract, they are becoming increasingly important for the role of the cecum in regulating immune responses in the gut – with implications for the entire body. If alpha-synuclein is formed there or if the annex produces the misfolded proteins that are the hallmark of Parkinson's disease, the presence or absence of an attachment should have an impact on the likelihood of a person developing the disease, the authors said based on the new study.

It was a hypothesis they could test if they could sift through the vast medical records of a vast population over many decades. In Sweden, a country with meticulous logging and a national registry of patients following from cradle to grave, they had two choices.

One was a database of detailed medical records for 1.6 million Swedes over an average of 54 years. Many of them had appendage atoms; far less Parkinson was diagnosed.

The analysis showed that early removal of the appendix was associated with a 20 percent reduction in the risk of developing Parkinson's disease.

The effect was intensified in people who lived in rural areas. It has been found that environmental pollutants increase the risk of Parkinson's, and it is widely believed that increased exposure to pesticides in rural areas explains the greater prevalence of the disease there. In this population, appendectomies were associated with a 25 percent lower risk of Parkinson's.

When the researchers looked at the time of an appendectomy, they found further evidence of a central role of the cecum in Parkinson's disease.

The decline in Parkinson's risk only became apparent when the cecum and the alpha-synuclein protein it contained were removed early in life. The removal of the appendix after the onset of the disease process, however, had no effect on the progression of the disease.

The authors of the study also examined tissue samples from 48 people who had undergone routine cecalectomy and were later undiagnosed. They found that 46 of the samples contained high levels of alpha-synuclein lumps similar to those in Lewy bodies, and that the age of the person from whom they were cut out did not seem to matter. For a disease in old age, this was a surprise.

In the lab, the researchers found that this excised tissue from healthy individuals can easily be formed into dangerous lumps in the brain of Parkinson's patients.

All this suggests a model in which rogue species of alpha-synuclein could accelerate the formation of misfolded clumps of protein, the authors write.

This does not mean, however, that the mystery of Parkinson's disease, first described in 1817 by Drs. James Parkinson was almost solved. (Coincidentally Parkinson described in 1812 the first acute appendicitis).

"There could be many causes," said co-author Viviane Labrie, a neurogeneticist at the Van Andel Research Institute in Grand Rapids, Michigan. The removal of the appendix "appears to be associated with a 20% reduction in this risk." , "This is a robust finding, but much remains to be explained.


"This work is well done and the size of the population used by these authors is very powerful," said Anumantha Kanthasamy, Parkinson's researcher at Iowa State University in Ames, who was not involved in the new research.

Kanthasamy emphasized that the association found in the study did not necessarily suggest that removal of the attachment directly lowered Sweden's risk of Parkinson's. The relationship could be quite complex: for example, the appendicitis attack that led to the removal of the organ could be the key to protecting a person.

"This adds to the concept that in Parkinson's disease, changes taking place in the peripheral nervous system, including the gut, are likely to occur much earlier than in classic brain pathology," he added. "And it contributes to our understanding that the gut and the peripheral nervous system are tightly connected to the brain."

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PHOTO (help with pictures: 312-222-4194): SCI PARKINSONS APPENDIX



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