Although Parkinson’s disease is generally considered a brain disorder, recent research has found that the body’s immune system may play a role in the development of this condition. Medical News Today spoke to Parkinson’s disease experts about why this might be.

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What role does the immune system play in Parkinson’s disease? Image credit: TonyBaggett/Getty Images.

Over the past few years, we have learned much more about the immune system and its impact on various diseases and aspects of our health.

While it helps protect the body from invading germs and viruses, the immune system also lends a hand in the overall health of different parts of the body such as the brain, heart, and gastrointestinal system.

And when a person’s immune system is not healthy, it leaves them susceptible to viral infections and other diseases. It can also impact their mental health and even cause sleeping issues.

In the case of the neurodegenerative condition Parkinson’s disease, researchers still do not know exactly what causes it. However, some researchers now believe that it may have direct ties with the health of a person’s immune system.

Medical News Today spoke with six experts to find out how the immune system might cause Parkinson’s disease. They also discuss how further research into this area might help scientists in developing new therapies and even protect against Parkinson’s disease.

And they offer advice on modifiable factors a person could change to help potentially influence the immune system and protect against the condition.

An immune system that does not function correctly is a main driver of systemic inflammation in the body.

Studies have shown that chronic inflammation may play a role in the development of a variety of conditions, including cardiovascular disease, diabetes, mental health concerns like depression, and brain-related diseases such as Alzheimer’s disease.

According to Dr. Julie Pilitsis, a board-certified neurosurgeon at Marcus Neuroscience Institute, established at Boca Raton Regional Hospital, part of Baptist Health, there is mounting evidence that inflammation plays a role in many diseases, including those of the brain.

“With age, our immune system becomes weaker and as the mean age for Parkinson’s disease is 60, age may explain how the immune system can be involved in some of the older patients affected,” she told Medical News Today.

“We also know that some of the genes that lead to Parkinson’s disease also lead to inflammation and that exposure to certain chemicals like pesticides heightens immune responses and can increase [the] risk of Parkinson’s disease.”

– Dr. Julie Pilitsis

“Immune system involvement in brain diseases is not unheard of,” added Dr. James Beck, senior vice president and chief scientific officer of Parkinson’s Foundation.

“Multiple sclerosis is primarily a brain disorder that involves and is treated by modulating the immune system,” he exemplified.

Nevertheless, “[w]hy the immune system is involved in Parkinson’s disease remains unanswered,” Dr. Beck told us.

“It could be the result of an autoimmune response where the immune system incorrectly identifies a brain protein as foreign and responds to it,“ he hypothesized. “It could be the result of insults elsewhere in the body — maybe even the brain — such as an infection, that triggers an immune response that involves the brain.”

If inflammation is involved in causing Parkinson’s disease, how exactly could that happen?

Dr. Osama Abu-hadid, a movement disorder specialist and assistant professor of neurology at the Parkinson’s Center at the Neuroscience Institute and the Department of Neurology at Hackensack University Medical Center and Hackensack Meridian School of Medicine, told MNT that there is currently no “hard” proof as to the exact mechanisms in which the immune system plays a role in the development of Parkinson’s disease.

“However, there are multiple theories along with associated studies that give some guidance,” he said. “One of the proposed mechanisms is impairment of the blood-brain barrier, allowing easier access of the immune system into the brain tissue, hence, exposing this system to native antigens it has not seen before.”

“Examples of such antigens include abnormal alpha-synuclein aggregates [and] the debris of dopaminergic neurons that underwent cell death due to energy failure or abnormal accumulation of non-functional proteins due to impaired cellular recycling pathways,” Dr. Abu-hadid added. “This exposure may agitate the immune system, both innate and adaptive, adding ‘fuel to the fire’.”

Dr. Alessandro Sette, professor at the Center for Autoimmunity and Inflammation and Center for Infectious Disease and Vaccine Research at La Jolla Institute, said his study from April 2020, published in Nature Communications, provides evidencethat the effect of the immune system on a certain part of the brain called the substantial nigra also plays a role in Parkinson’s disease development.

“When the substantia nigra is lost beyond a critical threshold and little of it remains, the clinical signs of cognitive loss and movement disorders become apparent, and the disease is diagnosed,” he explained. “But why is the substantia nigra lost?”

“Here the idea is that the immune system is involved, with a misplaced attack on the substantia nigra,” Dr. Sette continued. “Essentially the immune system mistakenly believes that the substantia nigra is foreign or dangerous and attacks it in a process called auto-immunity.”

And Dr. Tan Eng King, deputy chief executive officer of academic affairs and senior consultant in the Department of Neurology for the National Neuroscience Institute and one of the authors of a study on Parkison’s disease and the immune system, said that determining the exact cause-and-effect relationship between neuroinflammation and neurodegeneration in Parkinson’s disease is challenging as the effect likely occurs cumulatively years before neuronal loss and clinical manifestations.

“Several clinical studies using blood and cerebrospinal fluid in Parkinson’s disease patients showed immune cell problems supported by evidence of changes in pro-inflammatory and anti-inflammatory markers in patients compared to healthy individuals,” he explained to MNT.

“There is also a suggestion that gut bacteria in Parkinson’s disease are different from healthy people and their metabolites are linked to inflammatory processes that may promote neurodegeneration,” Dr. King added.

As further research unveils more about the link between the immune system and Parkinson’s disease, experts agree it may open doors for the development of new therapies or even protection against developing the disease.

“Understanding how the immune system may be a player in the neurodegeneration seen in the brains of people with Parkinson’s disease opens up a whole array of potential treatment options,” commented Dr. Rebecca Gilbert, vice-president and chief scientific officer for the American Parkinson Disease Association (APDA).

“Maybe we don’t have to stop the alpha-synuclein from accumulating if we can stop the immune response that is triggered [by] the accumulation,” she hypothesized.

“There are drugs already in clinical use that control the immune response,” Dr. Gilbert continued.

“It is possible that using existing medications that decrease inflammation or developing new medications that decrease inflammation can be used as treatments for Parkinson’s disease. In fact, APDA is funding research in this area. For example, Dr. Martine Tetrault is studying fat metabolism in peripheral blood immune cells of people with Parkinson’s disease and healthy controls to see if a fat-altering drug can reduce the inflammatory signals in these cells.”

– Dr. Rebecca Gilbert

“In my opinion, the big reason it is exciting to think about Parkinson’s disease beginning outside the brain in the immune system is that we could potentially identify people who are at risk for Parkinson’s disease prior to them having the disease,” Dr. Pilitsis added.

“To accomplish this, we would need to understand which patients are at risk by studying their genetics. Then we would need to watch for the early warning signs and start treatments either with existing anti-inflammatory medications or ideally with therapies that are personalized for the patient,” said Dr. Pilitsis.

Even though the exact cause of Parkinson’s remains unknown, there are various changes that people can make to their lifestyle that can help protect their immune system and potentially reduce the risk of Parkinson’s disease and similar conditions.

“It makes intuitive sense that instituting lifestyle modifications that potentially decrease inflammation may decrease [the] risk of Parkinson’s disease,” Dr. Gilbert said.

“Exercise, for example, has been shown to reduce inflammation and is probably one of the many reasons that exercise reduces the risk of Parkinson’s disease and also improves symptoms of established Parkinson’s disease,” she noted.

Dr. Pilitsis agreed exercise has been shown to have a positive effect on outcomes for those with Parkinson’s disease.

“Also we should avoid things like excessive alcohol and nicotine that we know have negative effects on the immune system,” she added. “[And] managing our stress as best as possible can slow and help maximize outcomes of many diseases.”

When it comes to what we eat, Dr. Gilbert said there is evidence that the Mediterranean and the MIND diets are good for brain health.

“The MIND diet emphasizes whole grains, vegetables, nuts, legumes, and berries,” she detailed. “Fish is the preferred protein and olive oil is the preferred fat. Recently a study was published that showed adherence to the MIND diet and the Mediterranean diets were associated with later onset of Parkinson’s disease.”