Can the environment cause Parkinson’s?
We know age and genetics play a role in Parkinson’s, but how does the world we live in impact on our risk of developing the condition?
Parkinson’s is a neurodegenerative condition affecting around 145,000 people in the UK. It develops when dopamine-producing cells in the brain stop working properly and, over time, are lost.
This much we know. But what we don’t know is what actually causes Parkinson’s. It’s often referred to as idiopathic Parkinson’s, which translates from the original Greek as “a disease of its own kind” — the cause is unknown.
Age is the biggest risk factor — most people who get Parkinson’s are aged 50 or over. As we age, damaging molecules called free radicals build up inside our bodies, causing the cells to become stressed. Energy-producing mitochondria (the cell’s batteries) may stop working properly, damaged proteins may accumulate, and, over time the cells may die. Research has shown that dopamine-producing brain cells seem to be particularly vulnerable to these changes seen with ageing, increasing the risk of Parkinson’s as we get older.
But, age isn’t the only player at the table. People under the age of 50 can get Parkinson’s too. This “early onset” Parkinson’s is often linked to very rare changes in certain genes, such as those involved in removing damaged proteins and helping mitochondria to work properly.
Can Parkinson’s be inherited?
In this blog, we explore how the genes we inherit can play a role in Parkinson’s.
In the majority of cases though, scientists currently agree that a complex interplay of environmental factors, lifestyle and variations in genetic makeup, interact to cause Parkinson’s disease. In most cases, these individual factors have a very subtle effect. But when they accumulate in the right way at the right time, the effects can be substantial.
In this blog, we’ll specifically investigate environmental factors in more detail.
Quick summary if you’re in a hurry
- Environmental factors — such as exposure to certain pesticides and other chemicals, infection, and even brain injury — have been found to slightly increase the risk of Parkinson’s.
- Some individuals may be more or less susceptible to different risk factors.
- It is almost impossible to identify the exact cause of Parkinson’s in most people.
Environmental risk factors for Parkinson’s
When we talk about the environment, we mean the world around us, and the pathogens (viruses and bacteria), toxic chemicals, and heavy metals that occupy it.
The idea that the environment could play a role in Parkinson’s first arose from an unusual medical case in the early 1980s. A group of heroin users in California took drugs from a batch contaminated with a substance called MPTP. Almost overnight, they experienced a type of parkinsonism that could be treated with L-dopa. The case hit the headlines, and sparked an interest in how chemicals and other environmental exposures could play a role in Parkinson’s.
Over the years, several more environmental factors have been suggested to influence the risk of developing Parkinson’s. While some associations remain unproven, other factors have repeatedly been found to either increase or decrease risk.
1. Pesticide use
Over the years, studies have linked Parkinson’s with rural living, farming, and well-water consumption. The common denominator in these studies is thought to be exposure to certain pesticides, including herbicides, insecticides, fungicides, and rodenticides.
Results have been variable, but the balance of research suggests that long term exposure to pesticides may slightly increase the risk of Parkinson’s. One study found that 5 and 10 years of pesticide exposure were associated with a 5% and 11% increase in the risk of developing Parkinson’s, respectively. Another study looking at occupational exposure to pesticides estimated that the risk may increase by 50% or more.
The pesticide with the strongest association is paraquat, a (now banned) herbicide with a chemical structure similar to MPTP (the Parkinson’s-causing substance that first appeared in the 80s.) Researchers in Canada have used this association to help us understand more about how pesticides could increase the risk of Parkinson’s. The team used stem cells to make two groups of dopamine-producing brain cells in the lab — “healthy” cells and some that carried a genetic mutation associated with Parkinson’s. They then exposed these new brain cells to some pesticides, including paraquat.
They found that the pesticides altered the way mitochondria move around, potentially affecting energy levels in the cell. Importantly, the cells carried the genetic mutation were more affected by the pesticide. These results add to the theory that our genetic makeup plays a huge role in how susceptible we are to toxic exposures in our environment, and may help to explain why most people exposed to pesticides do not go on to develop Parkinson’s.
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2. Other chemicals
Occupational exposure to chlorinated solvents used as cleaners and degreasers has also been suggested to increase the risk of Parkinson’s. In a study of twins, the risk of Parkinson’s was more than six times greater in the twin exposed to the industrial solvent, trichloroethylene (TCE), used as a degreaser and in dry cleaning. And animal studies have shown that TCE can cause loss of dopamine-producing nerve cells in the brain and stop mitochondria from working properly. However, other studies have not proved a definite link between exposure to solvents like TCE and an increased risk of Parkinson’s — the jury is still out.
Our bodies need manganese to work properly, which is why this element can be found in certain supplements. But too much can lead to toxicity and a condition known as “manganism”, characterised by Parkinson’s-like symptoms. Interestingly manganese accumulates in the basal ganglia of the brain — the area where brain cells are lost in Parkinson’s.
One study looking in welders in the US reported that exposure to manganese, found in welding fumes, increased the risk of developing manganism. And recent research suggests that this condition is caused by manganese triggering the misfolding of a protein in the brain cells, causing them to die.
3. Heavy metal exposure
Several studies have suggested a link between chronic exposure to mercury and the risk of Parkinson’s. Additionally, an early 1990s study in Michigan, US found that counties with active paper, chemical, iron, or copper related‐industries have been seen to have higher Parkinson’s death rates than counties without these industries, suggesting more people develop Parkinson’s if they have occupational exposure to heavy metals.
Researchers in the US looked in brain stem cells to understand how heavy metal exposure increases Parkinson’s risk. They found that when stem cells with a genetic mutation linked to Parkinson’s were exposed to copper, they were more likely to die when compared with healthy stem cells, highlighting again how environmental factors and genetics can interact to influence risk.
You cannot catch Parkinson’s — it’s not caused by a virus or bacteria. But, along with many other factors, infections — including hepatitis, H. pylori, and flu — do appear to play a role in risk.
One pioneering experiment neatly showed that severe flu can contribute to the loss of dopamine brain cells using an animal model of Parkinson’s. The US researchers investigated the effect of a particular strain of flu had on brain cells when it was combined with our old friend MPTP.
The researchers found that mice infected with the H1N1 strain of flu showed a 20% greater loss of these cells when treated with MPTP. They also showed that this extra effect caused by the combined effects of flu and the toxin could be reduced by vaccinating the mice against flu.
What this research shows is that while flu probably doesn’t cause the loss of dopamine brain cells directly, it can cause other factors to play a more significant role — this is known as the ‘multi-hit’ hypothesis. But, there’s currently no firm evidence that flu can increase the risk of developing Parkinson’s in later life.
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5. Brain injury
The association between severe head injury and an increased risk of Parkinson’s is fairly well established. One of the latest studies in this area looked at risk in veterans and discovered that even mild traumatic brain injury could increase the risk of developing Parkinson’s by 56% and that repeated injuries further increased risk. But more research is needed to understand how head injuries could trigger Parkinson’s.
So why do some people get Parkinson’s and others don’t?
Identifying risk factors for Parkinson’s doesn’t mean we know exactly what causes the condition. For environmental risk factors, some people who’ve been exposed to a potential risk factor for their whole lives may never develop Parkinson’s, while others with seemingly low levels of exposure do.
The best explanation is that some individuals may be more or less susceptible to different risk factors. As we’ve discussed a bit above, this likely has a lot to do with individual variability in our genetic makeup — the combination of many slight variations within our DNA may make us more or less susceptible to other risk factors.
Our susceptibility to environmental factors may also be influenced by how long and how often we are exposed, our diet and lifestyle, as well as age and gender. All of these different influences combine to make understanding individual risk very difficult. To complicate matters more, recent studies suggest that a person can be exposed to the risk factors years, or even decades, before Parkinson’s symptoms arise, making them harder to identify.
That’s not to say that research into risk factors isn’t important. Understanding what causes Parkinson’s is the first step toward prevention.
With the number of people being diagnosed with Parkinson’s increasing all the time, any initiatives to reduce the exposure to risk factors in our environment could help reduce the incidence of Parkinson’s in the population.