Parkinson’s disease causes

Last updated Aug. 18, 2023, by Marisa Wexler, MS
Fact-checked by Ana de Barros, PhD

Parkinson’s disease is a neurological disorder caused by the progressive dysfunction and death of neurons (nerve cells) that are responsible for making dopamine, called dopaminergic neurons. These neurons are primarily found in a part of the brain called the substantia nigra.

Dopamine is a neurotransmitter, a chemical that nerve cells use to communicate with each other. In Parkinson’s, the loss of dopamine-making cells leads to impaired dopamine signaling in the brain, which ultimately causes Parkinson’s symptoms.

Levels of another neurotransmitter called norepinephrine, which is made from dopamine, are also reduced in Parkinson’s and may contribute to symptoms, but the role of this neurotransmitter is less well-studied than that of dopamine.

It’s not known exactly what causes or triggers the death of dopamine-making cells in Parkinson’s. Many different factors, including abnormal protein clumps and inflammation in the brain, genetics, and exposure to toxic chemicals, may play a role.

Changes in the brain

While the exact changes that trigger the dysfunction of dopaminergic neurons remain incompletely understood, certain biological alterations in the brain are consistently found in Parkinson’s patients, and these are thought to play a central role in causing Parkinson’s and driving the disease’s progression.

Lewy bodies (protein clumps)

A hallmark feature of Parkinson’s is the formation of abnormal clumps of protein in brain cells. These clumps are sometimes referred to as Lewy bodies, named after the neurologist Friedrich Lewy who published the first formal description of them in 1912. Lewy bodies are a feature of several brain disorders.

Lewy bodies are toxic to nerve cells, and able to spread through the brain in a prion-like manner, meaning that protein clumps in one part of the brain can trigger more clumps to form in nearby areas. The spread of these toxic clumps throughout the brain is believed to be one of the key biological changes that drive nerve cell death and dysfunction in Parkinson’s disease.

While Lewy bodies usually contain more than one type of protein, in Parkinson’s patients, a main component of these toxic cell clumps is a protein called alpha-synuclein.

Finding ways to stop the toxic clumping of alpha-synuclein is being explored as a potential strategy to treat Parkinson’s, and several experimental therapies targeting this protein are currently in clinical development.

Lewy bodies are also found in people with Lewy body dementia, or LBD, which is characterized by cognitive problems. Dementia also can develop in people with Parkinson’s disease, and there can be clinical overlap between Parkinson’s and LBD. Typically, LBD is diagnosed when a person has Lewy bodies and cognitive problems, but does not have the motor symptoms that are required to confirm a Parkinson’s diagnosis.

Neuroinflammation

Neuroinflammation, or inflammation within the brain, is commonly seen in Parkinson’s and many other neurological disorders. Normally, inflammation helps to protect the brain from infection and repair injuries, but in Parkinson’s, out-of-control neuroinflammation may cause damage to nerve cells and contribute to disease progression.

It remains unclear whether abnormal inflammation is an initial trigger of Parkinson’s disease, or if inflammation goes haywire as a consequence of the ongoing nerve cell damage that characterizes the disease. In either case, it is widely accepted that neuroinflammation can help to drive nerve damage in the disease. Several experimental therapies are in development to treat Parkinson’s by reducing brain inflammation.

Gut-brain axis

Nerve cells in the brain connect out to other nerves that control the rest of the body, including the digestive system. The connection between the digestive system and the brain is commonly referred to as the gut-brain axis.

Digestive complaints are common among people living with Parkinson’s, and an emerging body of research has suggested that abnormalities in the gut may contribute to Parkinson’s. The basic thought is that abnormalities like protein clumps or inflammation in the digestive tract may act through the gut-brain axis to trigger similar changes in the brain.

This branch of research is still in relatively early stages. Scientists are working to understand in greater detail how the gut-brain axis may play a role in Parkinson’s development, and whether targeting this axis may be a viable strategy for treating the disease.

Genetic causes

In most people with Parkinson’s disease, there is no specific disease-related gene or a single genetic cause. However, about 5% to 10% of cases are caused by mutations in a single gene.

Given that these mutations can be passed from parents to their biological children, they are associated with Parkinson’s that runs in families. Of note, about 15% of Parkinson’s patients have a family history of the disease.

The manifestations of Parkinson’s disease, such as age at onset and specific symptoms, can vary widely even among people who carry the same disease-causing mutation. Still, generally speaking, most Parkinson’s-causing mutations are associated with early-onset disease, where symptoms appear before age 50. These genes include:

• SNCA
• GBA
• PINK1
• PARK7
• PRKN
• PLA2G6
• ATP13A2
• FBXO7
• POLG
• DNAJC6
• SYNJ1
• VPS13C.

Mutations in a few other genes tend to cause Parkinson’s after 50 years of age, which is more typical for age of onset. These include LRRK2, VPS35, and CHCHD2.

While mutations in the genes GBA and LRRK2 represent the two most common genetic causes of Parkinson’s disease, not everyone who has a mutation in one of these genes will develop the disease. This phenomenon, where a mutation can cause disease in some people but not others, is known as “incomplete penetrance.”

Dozens of other genetic variations have been linked with Parkinson’s risk, but they do not cause the disease outright.

Risk and environmental factors

Several environmental factors are believed to increase a person’s risk of developing Parkinson’s, ranging from past physical trauma to air pollutants. Risk factors such as age and sex also seem to play a role.

Age and sex

Parkinson’s usually develops in the latter decades of life — most people develop the disease around age 60 or older. Research suggests life expectancy is mainly reduced if the disease is diagnosed before the age of 70.

The disease is roughly twice as common in men than women, though women tend to have faster disease progression. There may also be differences in common symptoms and responses to treatment, though the reasons for these sex-based differences are poorly understood.

Traumatic brain injury

Traumatic brain injury (TBI) occurs when a physical injury such as a violent blow or jolt to the head leads to brain damage. Studies have shown that the risk of Parkinson’s is increased by more than 50% in people who have a history of mild traumatic brain injury, and the risk is nearly doubled in people who have a history of more severe TBI.

Environmental toxins, agricultural chemicals, and air pollution

Exposure to different types of toxins and chemicals have been associated with an increased risk of Parkinson’s disease. These include:

• trichloroethylene (TCE), a solvent that’s been used in many industry applications
• a group of chemicals called polychlorinated biphenyls (PCBs)
• pesticides and herbicides, particularly an herbicide called paraquat
• heavy metals such as iron, mercury, manganese, copper, and lead.

Furthermore, several studies have shown the risk of Parkinson’s is increased in people who are more exposed to air pollution.

Employment and location

Certain occupations have been tied to a higher risk of Parkinson’s disease, particularly jobs such as agricultural work that expose people to toxins linked to increased disease risk. Exposure to a herbicide known as Agent Orange by the U.S. military during the Vietnam War has also been associated with an increased Parkinson’s risk.

Some studies have suggested that high-stress jobs may increase the risk of developing Parkinson’s, but this connection has not been conclusively proven.

Parkinson’s prevalence also varies in different locations. For example, the disease is more common in some U.S. states than others, though the reasons for these differences are not well understood.

Drugs and medication

Certain medications can cause Parkinson’s-like symptoms as a side effect, a condition referred to as drug-induced parkinsonism. This is especially common with medicines that work by reducing dopamine signaling, which include several therapies for schizophrenia and other psychotic disorders. Generally, drug-induced parkinsonism will resolve after the medication is stopped.

Prevention

While it is currently impossible to prevent Parkinson’s, some steps may help to reduce the risk of developing the disease. These largely involve avoiding known risk factors, such as limiting exposure to chemicals and taking safety measures to avoid head injury.

Furthermore, several studies have suggested people who are more physically active are less likely to develop Parkinson’s, so getting regular exercise may help to reduce the disease risk.

Consuming caffeine (the chemical in coffee that causes feelings of wakefulness) and smoking tobacco cigarettes each have been linked with a reduced risk of Parkinson’s. However, since caffeine and tobacco may cause negative health effects, especially when consumed in high quantities, it is generally not recommended that people consume these chemicals for the sole purpose of lowering their Parkinson’s risk.

Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.