Chlorpyrifos tied to 2.5-fold Parkinson’s risk, UCLA study finds

Long-term residential exposure to the pesticide chlorpyrifos was linked to more than 2.5 times the risk of Parkinson’s disease, UCLA Health researchers found, and laboratory experiments suggested a mechanism for how the chemical harms the brain.

The study, published in Molecular Neurodegeneration, examined 829 people diagnosed with Parkinson’s disease and 824 people without the condition, all enrolled in the university’s Parkinson’s Environment and Genes study. The researchers combined California pesticide application records with participants’ residential and workplace address histories to estimate exposure over time.

People with prolonged residential exposure to chlorpyrifos had more than 2.5 times the risk of Parkinson’s compared with those with no such exposure. The population analysis could not establish that the pesticide directly caused the disease.

Chlorpyrifos has been used in agriculture for decades. Its residential use was banned in the United States in 2001, and agricultural applications faced additional restrictions in 2021. It remains in use on many crops in the U.S. and is widely applied in other countries.

Parkinson’s disease affects nearly one million Americans. It gradually damages brain cells involved in movement, often causing tremors, muscle stiffness, slowed movement and coordination difficulties, and is marked by the loss of neurons that produce dopamine.

Mouse and zebrafish experiments

The team exposed mice to chlorpyrifos in aerosol form for 11 weeks, an approach designed to resemble a common way people may encounter pesticides. The exposed mice developed movement difficulties and lost dopamine-producing neurons, and the researchers also detected brain inflammation and abnormal accumulations of a protein called alpha-synuclein.

The researchers then turned to zebrafish to investigate how chlorpyrifos harms neurons. Their experiments pointed to a disruption in autophagy, a cellular maintenance process that removes damaged proteins and other unwanted material. When chlorpyrifos interfered with this cleanup system, damaged material accumulated inside neurons.

When the researchers restored the cleanup process or removed synuclein protein in their experiments, the neurons were protected from damage. The protective effects have so far been demonstrated only in laboratory models, and additional research will be needed to determine whether enhancing autophagy can prevent or reduce pesticide-related brain damage in humans.

Dr. Jeff Bronstein, professor of Neurology at UCLA Health and the study’s senior author, said the work identifies a specific chemical rather than treating all pesticides as one category.

“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. “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.”