Parkinson’s disease causes
Reviewed by Parkinson’s disease involves the progressive dysfunction and death of dopamine-producing nerve cells, primarily in the brain’s substantia nigra. Dopamine helps control smooth, purposeful movement. Its loss causes Parkinson’s symptoms, including tremor, rigidity, slowed movement, and postural instability.
Dopamine also helps produce norepinephrine, a chemical messenger that regulates automatic functions such as blood pressure, sweating, and digestion. Lower norepinephrine levels may contribute to nonmotor symptoms.
The cause of dopamine-producing cell death is not fully understood, but biological, genetic, and environmental factors may play a role.
Biological changes in the brain
Most cases of Parkinson’s disease are idiopathic, meaning the exact cause is unknown. Genetics, aging, exposure to certain environmental factors, and changes in the brain all contribute to the destruction of dopamine-producing cells, leading to Parkinson’s disease symptoms.
Certain biological changes consistently appear in the brains of people with Parkinson’s. These changes are thought to play a central role in causing Parkinson’s and driving the disease’s progression.
Lewy bodies and alpha-synuclein accumulation
A hallmark feature of Parkinson’s is the formation of abnormal protein clumps in the brain, commonly referred to as Lewy bodies after the neurologist who discovered them.
The main component of Lewy bodies is alpha-synuclein, a protein that helps nerve cells communicate. In Parkinson’s disease, alpha-synuclein misfolds into clumps that build up in nerve cells, eventually causing them to die.
These misfolded protein clumps can spread through the brain in a prion-like manner, meaning clumps in one part of the brain may cause 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.
Researchers are currently testing ways to prevent alpha-synuclein from clumping as a potential strategy to treat Parkinson’s. Several experimental therapies targeting this protein are currently in clinical development.
Lewy bodies appear in several brain conditions, including Parkinson’s disease and Lewy body dementia. Doctors use the “one-year rule” to tell dementia with Lewy bodies apart from Parkinson’s disease dementia:
- Dementia with Lewy bodies: Cognitive decline and dementia starting before or within one year of motor symptoms.
- Parkinson’s disease dementia: Motor symptoms are present for more than one year before significant cognitive decline or dementia develops.
Neuroinflammation and immune response
Neuroinflammation, or inflammation in the brain, commonly occurs in Parkinson’s disease. Although inflammation normally protects the body against illness and injury, long-term inflammation can damage healthy tissue and may contribute to nerve cell damage and disease progression.
People with Parkinson’s show higher levels of brain inflammation, which is linked to symptoms such as memory and thinking problems. Whether inflammation triggers Parkinson’s or results from cell damage remains unclear, but ongoing research aims to find ways to reduce brain inflammation.
The gut-brain connection
Digestive issues, including nausea and constipation, frequently affect people with Parkinson’s. Constipation often starts years before movement symptoms appear, suggesting a potential link between the gut and the brain.
The gut-brain axis allows two-way communication between these organs. Clumps of alpha-synuclein have been found in the gastrointestinal tract of people with Parkinson’s. Researchers are investigating whether these clumps can travel from the gut to the brain and trigger similar changes.
Research into the gut-brain axis in Parkinson’s disease remains in its early stages but may lead to treatments targeting this connection.
Genetic causes and risk genes
Genetic variants are DNA changes that can cause Parkinson’s disease or increase its risk. Most people with Parkinson’s have no known single-gene variant that explains their condition, though pathogenic variants in a single gene account for about 5% to 10% of cases.
Some variants pass down from parents to children, and about 15% of people with Parkinson’s have a family history. Inheritance patterns vary by gene:
- Autosomal dominant pattern: One copy of the variant from one parent is enough to cause the disease.
- Autosomal recessive pattern: Two copies of the variant — one from each parent — are needed to cause the disease.
Some genetic variants associated with Parkinson’s exhibit “incomplete penetrance,” meaning not everyone who inherits the variant goes on to develop the disease. A complex interaction of genetic, environmental, and other factors likely plays a role in determining who develops Parkinson’s.
The most commonly associated genes with Parkinson’s are LRRK2 and GBA, but dozens of genes are implicated, including the following.
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| Gene | Role in Parkinson’s | Inheritance pattern | Typical features |
|---|---|---|---|
| GBA | Most common gene associated with the risk of developing Parkinson’s; variants found in 5% to 10% of people with Parkinson’s | Not typically classified as dominant or recessive for Parkinson’s | Earlier onset; greater risk for rapid progression of dementia; greater motor difficulties |
| LRRK2 | Second most common Parkinson’s-related gene variants found in 1% of all people with Parkinson’s and 5% of those with a family history | Dominant | Potentially less common cognitive decline and some other nonmotor symptoms; motor symptoms similar to those of idiopathic Parkinson’s disease; potentially slower motor symptom progression |
| PRKN | Most common cause of early-onset Parkinson’s | Recessive | Early symptoms such as bradykinesia and rigidity; lower risk of dementia |
| PINK1 | Second most common cause of early-onset Parkinson’s | Recessive | Early symptoms such as bradykinesia and rigidity; nonmotor symptoms such as cognitive decline are more common; slow disease progression |
| PARK7 | Rare cause of early-onset Parkinson’s found in fewer than 1% of people with the condition | Recessive | Similar to non-genetic types of Parkinson’s |
| SNCA | Rare cause of early-onset Parkinson’s | Dominant | Early nonmotor symptoms, such as cognitive decline; more rapid progression |
| VPS35 | Rare variant found in Parkinson’s disease | Dominant | Milder symptoms; slower progression |
As researchers identify additional genetic variants associated with Parkinson’s disease, they may discover new treatment approaches that target those specific gene changes.
Environmental risk factors for Parkinson’s disease
Environmental factors, including past physical trauma and air pollution, may increase Parkinson’s risk. Factors that cannot be changed, such as age and sex, also play a role.
- Age: Aging is the greatest risk factor, with symptoms usually starting around 60 or older. About 10% to 20% of people experience symptoms before age 50, known as early-onset Parkinson’s. Getting diagnosed before age 70 can lead to a greater reduction in overall life expectancy.
- Sex: Parkinson’s affects men about 1.5 times more often, although women may experience faster disease progression. Symptoms and treatment responses differ between men and women for reasons researchers are still studying.
Traumatic brain injury
Traumatic brain injury (TBI) happens after a physical blow or jolt to the head, which can cause symptoms including loss of consciousness and memory.
In a study of military veterans, a history of mild TBI was associated with a more than 50% increased risk of Parkinson’s, with even higher risk linked to severe TBI.
Environmental toxins, agricultural chemicals, and air pollution
Exposure to certain chemicals and toxins is associated with an increased risk of Parkinson’s disease. These include:
- industrial chemicals and solvents, such as trichloroethylene and a group of chemicals called polychlorinated biphenyls
- pesticides and herbicides, particularly an herbicide called paraquat
- heavy metals, such as iron, mercury, manganese, copper, and lead
In addition, several studies have shown that the risk of Parkinson’s is increased in people who have long-term exposure to air pollution.
Occupation
Certain jobs carry a higher risk of Parkinson’s disease, especially agricultural work that involves frequent contact with chemical toxins. Exposure to a herbicide known as Agent Orange by the U.S. military during the Vietnam War has also been associated with an increased risk of Parkinson’s.
While some studies suggest high-stress jobs might increase the risk of developing Parkinson’s, the evidence is limited.
Geographic location
Parkinson’s rates vary by geographic region. For instance, the disease occurs more frequently in certain parts of the United States, such as the Rust Belt in the Northeast and Midwest. Although these regional differences are not fully understood, variations in local populations and toxin exposure likely explain the pattern.
Drugs and medication
Certain medications, especially those that block dopamine signaling to treat psychiatric conditions, can cause Parkinson’s-like symptoms called drug-induced parkinsonism. These symptoms usually go away after stopping the medication.
Can Parkinson’s disease be prevented?
Although no proven strategy completely prevents Parkinson’s, several healthy habits can help reduce overall risk:
- Avoid known risk factors: Limit exposure to industrial chemicals and take safety measures to prevent head injury.
- Exercise regularly: Research suggests that staying physically active may reduce the risk of Parkinson’s disease, with aerobic exercise potentially being particularly beneficial.
- Eat a well-balanced diet: Plant-based, whole foods rich in antioxidants support brain health and may help reduce the risk of Parkinson’s. In addition, consuming caffeine is tied to a lower risk of Parkinson’s.
Some studies show that cigarette smokers have lower rates of Parkinson’s disease. However, researchers do not fully understand why, and smoking causes severe, life-threatening health problems. Because of these risks, health professionals strongly advise against smoking to lower the risk of Parkinson’s.
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 other 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.
