Common pesticide chlorpyrifos linked to more than 2.5 times Parkinson's risk

Parkinson's disease affects nearly one million Americans, progressively damaging brain cells involved in movement. Researchers have increasingly focused on environmental exposures, particularly pesticides, as possible contributors, and the new study identifies a specific chemical rather than treating pesticides as a class.

The UCLA team examined data from 829 people with Parkinson's disease and 824 controls enrolled in the university's long-running Parkinson's Environment and Genes study. By combining California's detailed pesticide application records with participants' residential and work addresses, they estimated chlorpyrifos exposure over time. The result: those with prolonged residential exposure had more than 2.5 times the risk of Parkinson's.

To investigate whether chlorpyrifos could produce brain damage, the researchers exposed mice to aerosolised chlorpyrifos for 11 weeks, using a route intended to resemble a common way people may encounter pesticides in the environment. The treated mice developed movement difficulties and lost dopamine-producing neurons, a hallmark of Parkinson's. Their brains also showed inflammation and abnormal clumps of the protein alpha-synuclein, which are closely tied to the disease.

Further experiments in zebrafish pointed to a breakdown in autophagy, the cellular process that removes damaged proteins and other waste. When chlorpyrifos interfered with this internal recycling system, damaged material accumulated inside neurons. Restoring the autophagy process or removing synuclein protected the cells from damage, suggesting a potential therapeutic target.

“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, 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.”

Chlorpyrifos has been used extensively in agriculture for decades. Its residential use was banned in the United States in 2001, and agricultural applications faced additional restrictions in 2021, but it remains in use on many crops domestically and widely overseas. The findings raise the possibility of therapies that boost the brain's natural cleanup systems, though further research is needed to determine whether such an approach could work in humans.

The findings could help identify people with a history of substantial pesticide exposure who might benefit from neurological monitoring, as researchers work toward treatments that slow or prevent Parkinson's progression.