A UCLA Health study reports that people with long-term residential exposure to the pesticide chlorpyrifos had more than a 2.5-fold higher likelihood of developing Parkinson’s disease. The research, published in Molecular Neurodegeneration, pairs human exposure estimates with animal and zebrafish experiments that found dopamine-neuron damage and disruptions to the brain’s protein “cleanup” system.
Researchers at UCLA Health examined data from 829 people diagnosed with Parkinson’s disease and 824 people without the condition, all participants in UCLA’s Parkinson’s Environment and Genes study.
To estimate exposure, the team combined California pesticide-use records with participants’ residential and workplace location histories to reconstruct likely chlorpyrifos exposure patterns over many years.
The analysis found that individuals with long-term residential exposure to chlorpyrifos had more than a 2.5 times greater risk of developing Parkinson’s disease than those with little or no exposure.
Chlorpyrifos has been widely used in agriculture for decades. Its residential use was banned in 2001, and restrictions on agricultural applications were introduced in 2021. Despite those limits, UCLA said the chemical continues to be used on a variety of crops in the United States and remains common in other parts of the world.
The researchers also conducted laboratory tests to probe potential biological mechanisms. In one set of experiments, mice inhaled aerosolized chlorpyrifos for 11 weeks, using an exposure approach the researchers said was designed to mimic how people typically encounter the chemical. The mice developed movement problems and lost dopamine-producing neurons, and researchers observed brain inflammation and an abnormal buildup of alpha-synuclein, a protein that forms clumps in the brains of people with Parkinson’s.
In zebrafish experiments, the researchers found that chlorpyrifos disrupted autophagy, the cellular process that clears damaged proteins. When the team restored this process—or removed synuclein protein—the neurons were protected from injury.
“\"This study establishes chlorpyrifos as a specific environmental risk factor for Parkinson's disease, not just pesticides as a general class,\"” said Dr. Jeff Bronstein, a professor of neurology at UCLA Health and the study’s senior author. “\"By showing the biological mechanism in animal models, we've demonstrated that this association is likely causal. The discovery that autophagy dysfunction drives the neurotoxicity also points us toward potential therapeutic strategies to protect vulnerable brain cells.\"”
Parkinson’s is a progressive neurological disorder that can cause tremors, muscle stiffness and increasing difficulty with movement. UCLA noted that nearly one million people in the United States are living with the condition.
The researchers said identifying specific chemicals associated with higher Parkinson’s risk could help guide prevention efforts and might help identify individuals who could benefit from earlier neurological monitoring or future protective therapies. They also said future research may examine whether other commonly used pesticides affect the brain in similar ways.
