What Causes Parkinson's Disease?

Medically reviewed by Nicholas R. Metrus, MD

Parkinson's disease has two likely causes. The first is the death of nerve cells in the substantia nigra of the basal ganglia region of the brain, which is the area that controls movement. The second is the accumulation of alpha-synuclein protein, forming deposits in intraneuronal inclusions called Lewy bodies. These factors lead to the insufficient production of dopamine (a brain chemical that helps regulate movement).

Parkinson's disease is a chronic and progressive neurological disorder. Symptoms include trembling, slow or interrupted movements (bradykinesia), rigidity, and postural problems.

Parkinson's disease is thought to arise due to a combination of genetic and environmental factors. Though this condition isn't inherited, having certain genes can increase your susceptibility. Several lifestyle factors and exposure to certain toxins can also increase the risk of developing the disorder.

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Theories

More research is needed to determine the exact causes of Parkinson's disease. Several theories have been proposed. The disorders likely arise due to a combination of certain genetic, environmental, and behavioral factors.

Genetic Factors

Genetic mutations are thought to play a significant role in the development of Parkinson's disease in about 15% of cases. Genetics alone is rarely the cause of Parkinson's disease, but it can increase the risk of developing it when combined with other factors.

Parkinson's disease has been linked to specific mutations of the synuclein alpha (SNCA) and leucine-rich repeat kinase 2 (LRRK2) genes, among others. These mutations allow synuclein alpha to build up and form Lewy bodies, impacting the natural release of a brain chemical called dopamine. Dopamine plays an important role in helping to control voluntary and involuntary movements.

Mitochondrial Dysfunction

Another hypothesis as to the cause of Parkinson's disease is dysfunction of the mitochondria. This part of a cell is involved with respiration and energy production. Dysfunction in the nerve cells of the substantia nigra leads to their degradation and death. This likely occurs alongside other factors in the disease, such as exposure to toxins in the environment and lifestyle risk factors.

Oxidative Stress

Reactive oxygen species (ROS) are naturally occurring molecules in the cell. ROS play a role in cellular communication, helping areas of the body communicate with each other.

Elevated levels of ROS, which usually occur as a result of mitochondrial dysfunction, can cause oxidative stress. Oxidative stress can damage or even kill necessary cells. Certain stressors, such as exposure to certain environmental toxins and metals, boost ROS. Damage and degeneration of cells can lead to Parkinson's disease.

Exposure to Toxins

More research is needed, but some evidence suggests that Parkinson's disease can arise due to exposure to environmental toxins. This exposure can trigger oxidative stress. Research has found a link between exposure to certain pesticides, such as paraquat and rotenone, and oxidative stress.

Elevated levels of iron may have a similar effect. Iron plays a role in cellular metabolism. Significantly elevated iron levels have been found in the brains of those with Parkinson's disease.

Is Parkinson's Disease Hereditary?

Some rare types of Parkinson's disease cases are hereditary, or passed from parent to child. Mutations of several genes, including SNCA and LRRK2, are directly inherited, causing monogenic cases. These cases occur because of a mutation in a single gene. Research has found the inheritance pattern to vary.

Some forms of Parkinson's disease are autosomal dominant, meaning only one parent with the mutation is needed to pass the disease along. Other types are autosomal recessive, in which the disease arises only when both parents have it.

Having a mutated gene may not always lead to Parkinson's disease in these cases. A study published in 2020 of twins estimated the overall heritability, or the extent to which genetic differences lead to the condition, to be 30%. These results indicate that other factors are more significant.

About nine out of 10 cases of Parkinson's disease aren't directly linked to gene mutations. Further research is needed to fully understand the genetic component of this condition.

Who Gets Parkinson's Disease?

It's estimated that 0.3% of adults over 40 worldwide develop Parkinson's disease. Some populations are more likely to develop this condition:

• Age: Aging increases the risk of developing this disorder. Parkinson's disease occurs in less than 1% of those aged 45–54. The prevalence rises to 4% in men and 2% in women aged 85 and older.

• Ethnicity: Certain ethnicities and races may be more prone to develop Parkinson's disease. Ashkenazi Jewish people are susceptible to a genetic form of the disorder. Some evidence suggests elevated rates among Inuit, Alaska Native, and Native American populations.

• Sex: Men are twice as likely as women to develop Parkinson's disease.

Risk Factors

Further research is needed to fully grasp factors that increase the risk of Parkinson's disease. Getting physical activity and regularly consuming caffeine may protect against the disorder.

Head Trauma

A history of head trauma due to falls or contact sports has been associated with Parkinson's disease. Research has found a mild to moderate effect, with the risk of developing the disorder increasing with the number of incidents.

Environmental Exposure

Some evidence suggests that being exposed to chemicals and toxins can increase Parkinson's disease. These include:

• Airborne toxins: Living in urban or industrial areas is a risk factor. Regular exposure to air or environments with high levels of pollutants, copper, manganese, and lead may increase your chances.

• Pesticides and herbicides: Working with pesticides or herbicides, as in agricultural or landscaping work, has been found to increase the risk of developing Parkinson's disease.

• Solvents: Working with or being regularly exposed to certain industrial solvents or paints, especially trichloroethylene (used to make refrigerants and as a metal degreaser), might increase risk.

High Dairy Consumption

Some evidence suggests higher rates of Parkinson's disease among those who consume excess dairy. A review published in 2014 noted associations between higher rates of milk, cheese, and other product consumption and disease onset. This effect was more pronounced among men.

Insufficient Vitamin D

Another risk factor for Parkinson's disease is not getting enough vitamin D. Research has linked not getting enough exposure to direct sunlight, a common source of this vitamin, to increased chances of developing the disorder.

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A Quick Review

Parkinson's disease is a progressive neurodegenerative disorder characterized by tremors and motor difficulties. It is likely caused by the death of nerve cells in the part of the brain responsible for movement and the formation of deposits in intraneuronal inclusions called Lewy bodies.

The exact cause for why this happens is unknown. A combination of genetic and environmental factors is thought to lead to it. Risk factors for Parkinson's disease include older age and exposure to pesticides and airborne toxicants, among others.

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