Monday December 10, 2018

Lipid Accumulation in The Brain May Be an Early Sign of Parkinson’s Disease

Lipid accumulation in brain may indicate Parkinson's risk

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Elevated levels of certain types of lipids, or fat molecules, in the brain may be an early sign of Parkinson’s disease, new research has found.

This finding, published online in the journal Neurobiology of Aging, could have significant implications for identifying patients who may be at risk of developing Parkinson’s disease and for the early treatment of the disease.

Parkinson’s disease is a degenerative, progressive disorder characterised by the dramatic reduction of nerve cells, particularly dopamine neurons that are involved in movement initiation, in an area of the brain called the substantia nigra.

“This (study) potentially provides an opportunity to treat lipid changes early on in Parkinson’s disease and protect nerve cells from dying, as well as the chance to use the lipid levels as biomarkers for patients at risk,” said study lead author Penny Hallett from McLean Hospital, an affiliate of Harvard Medical School in the US.

For many years now, the loss of the nerve cells has been attributed to the toxic accumulation of the protein alpha-synuclein.

Representational image
Representational image. Wikimedia Commons

In the past 15 years, however, researchers have been studying an interesting relationship between the risk of developing the disease and mutations that lead to loss of function in the glucocerebrosidase (GBA) gene.

Scientists at the Neuroregeneration Research Institute at McLean Hospital had previously shown that there is an elevation of a class of lipids, called glycosphingolipids, in the substantia nigra of patients with Parkinson’s disease.

Since ageing is the most significant risk factor for developing Parkinson’s disease, the team measured the levels of glycosphingolipids in the ageing brain, using young and old mice.

They found that the same glycosphingolipids that are increased in the brains of Parkinson’s disease patients are also elevated in the brains of ageing mice.

Also Read: This New App Can Score Parkinson’s Severity

These findings showed that both genetics (GBA gene mutation) and ageing can cause the same lipid elevations in the brain that are demonstrated in Parkinson’s disease pathology.

“These results lead to a new hypothesis that lipid alterations may create a number of problems inside nerve cells in degenerative ageing and Parkinson’s disease, and that these changes may precede some of the more obvious hallmarks of Parkinson’s disease, such as protein aggregates,” Hallett said.  IANS

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Risk Of Parkinson’s Disease And Appendix Removal Linked: Scientists

There are other unrelated risks for Parkinson's disease, such as suffering a traumatic brain injury.

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A researcher takes a tissue sample from a human brain at the Multiple Sclerosis and Parkinson’s UK Tissue Bank, at Imperial College London, Britain June 3, 2016. An appendix, often considered useless, seems to store an abnormal protein, which if it makes its way into the brain, has been found to become a hallmark of Parkinson's. VOA

Scientists have found a new clue that Parkinson’s disease may get its start not in the brain but in the gut – maybe in the appendix.

People who had their appendix removed early in life had a lower risk of getting the tremor-inducing brain disease decades later, researchers reported Wednesday.

Why? A peek at surgically removed appendix tissue shows this tiny organ, often considered useless, seems to be a storage depot for an abnormal protein – one that, if it somehow makes its way into the brain, becomes a hallmark of Parkinson’s.

The big surprise, according to studies published in the journal Science Translational Medicine: Lots of people may harbor clumps of that worrisome protein in their appendix – young and old, people with healthy brains and those with Parkinson’s.

Parkinson's Disease
Parkinson’s Disease Gets Awareness From Various Events. Flickr

But don’t look for a surgeon just yet.

“We’re not saying to go out and get an appendectomy,” stressed Viviane Labrie of Michigan’s Van Andel Research Institute, a neuroscientist and geneticist who led the research team.

After all, there are plenty of people who have no appendix yet still develop Parkinson’s. And plenty of others harbor the culprit protein but never get sick, according to her research.

The gut connection

Doctors and patients have long known there’s some connection between the gastrointestinal tract and Parkinson’s. Constipation and other GI troubles are very common years before patients experience tremors and movement difficulty that lead to a Parkinson’s diagnosis.

Wednesday’s research promises to re-energize work to find out why, and learn who’s really at risk.

Parkinson's Disease
GREAT MANCHESTER RUN 2010.Parkinson’s UK Runners

“This is a great piece of the puzzle. It’s a fundamental clue,” said Dr. Allison Willis, a Parkinson’s specialist at the University of Pennsylvania who wasn’t involved in the new studies but says her patients regularly ask about the gut link.

Parkinson’s Foundation chief scientific officer James Beck, who also wasn’t involved, agreed that “there’s a lot of tantalizing potential connections.”

He noted that despite its reputation, the appendix appears to play a role in immunity that may influence gut inflammation. The type of bacteria that live in the gut also may affect Parkinson’s.

But if it really is common to harbor that Parkinson’s-linked protein, “what we don’t know is what starts it, what gets this whole ball rolling,” Beck said.

For years, scientists have hypothesized about what might cause the gut-Parkinson’s connection. One main theory: Maybe bad “alpha-synuclein” protein can travel from nerve fibers in the GI tract up the vagus nerve, which connects the body’s major organs to the brain. Abnormal alpha-synuclein is toxic to brain cells involved with movement.

Parkinson's Disease
That’s a crucial finding because it means merely harboring the protein in the gut isn’t enough to trigger Parkinson’s. Flickr

There have been prior clues. People who decades ago had the vagus nerve cut as part of a now-abandoned therapy had a reduced risk of Parkinson’s. Some smaller studies have suggested appendectomies, too, might be protective – but the results were conflicting.

Labrie’s team set out to find stronger evidence.

First, the researchers analyzed Sweden’s huge national health database, examining medical records of nearly 1.7 million people tracked since 1964. The risk of developing Parkinson’s was 19 percent lower among those who had their appendix surgically removed decades earlier.

One puzzling caveat: People living in rural areas appeared to get the benefit. Labrie said it’s possible that the appendix plays a role in environmental risk factors for Parkinson’s, such as pesticide exposure.

Further analysis suggested people who developed Parkinson’s despite an early-in-life appendectomy tended to have symptoms appear a few years later than similarly aged patients.

parkinson's disease
The main symptoms of Parkinson’s disease are tremor, slowness of movement (bradykinesia) and muscle stiffness or rigidity. Wikimedia commons

A common protein

That kind of study doesn’t prove that removing the appendix is what reduces the risk, cautioned Dr. Andrew Feigin, executive director of the Parkinson’s institute at NYU Langone Health, who wasn’t involved in Wednesday’s research.

So next, Labrie’s team examined appendix tissue from 48 Parkinson’s-free people. In 46 of them, the appendix harbored the abnormal Parkinson’s-linked protein. So did some Parkinson’s patients. Whether the appendix was inflamed or not also didn’t matter.

That’s a crucial finding because it means merely harboring the protein in the gut isn’t enough to trigger Parkinson’s, Labrie said. There has to be another step that makes it dangerous only for certain people.

“The difference we think is how you manage this pathology,” she said – how the body handles the buildup.

Parkinson’s disease is named after Dr James Parkinson (1755-1824), the doctor that first identified the condition. Wikimedia commons
Parkinson’s disease is named after Dr James Parkinson (1755-1824), the doctor that first identified the condition. Wikimedia commons

Her team plans additional studies to try to tell.

The reservoir finding is compelling, Feigin said, but another key question is if the abnormal protein also collects in healthy people’s intestines.

Also Read: Travelling To Space May Alter Brain, Says Study

And Penn’s Willis adds another caution: There are other unrelated risks for Parkinson’s disease, such as suffering a traumatic brain injury.

“This could be one of many avenues that lead to Parkinson’s disease, but it’s a very exciting one,” she said. (VOA)