UCLA Study Links Common Pesticide Chlorpyrifos to More Than Double the Risk of Getting Parkinson’s Disease

LOS ANGELES — A widely used agricultural pesticide may pose a far greater threat to brain health than previously understood, according to new research from UCLA Health that links long-term exposure to the chemical chlorpyrifos with a sharply elevated risk of developing Parkinson’s disease, while also identifying a specific biological mechanism that may explain why.

The study, published in the journal Molecular Neurodegeneration, found that people with long-term residential exposure to chlorpyrifos had more than 2.5 times the risk of developing Parkinson’s disease compared with those who were not exposed. The research combined human population data with laboratory experiments in mice and zebrafish, providing both an epidemiological link and biological evidence to support it.

Researchers analyzed data from 829 people diagnosed with Parkinson’s disease and 824 individuals without the condition, all enrolled in UCLA’s long-running Parkinson’s Environment and Genes study. The cohort was drawn from three agricultural counties in central California — Kern, Fresno and Tulare — with participants recruited in two waves, one from 2000 to 2007 and a second from 2009 to 2015. To estimate each participant’s cumulative exposure to chlorpyrifos, the research team combined California’s Pesticide Use Report database, which has tracked agricultural chemical use in the state since 1972, with detailed residential and workplace address histories spanning decades.

Dr. Jeff Bronstein, a professor of Neurology at UCLA Health and the study’s senior author, said the findings move beyond general associations between pesticides and Parkinson’s to implicate one chemical specifically.

“This study establishes chlorpyrifos as a specific environmental risk factor for Parkinson’s disease,” Bronstein said, adding that the work does not simply lump pesticides together as a broad category but isolates this compound’s distinct contribution to disease risk.

To understand how chlorpyrifos might cause that damage, researchers turned to laboratory experiments. Mice were exposed to aerosolized chlorpyrifos through inhalation for 11 weeks, a method designed to mirror how people in agricultural communities are most commonly exposed to the chemical in real-world settings. The exposed mice developed movement problems and lost dopamine-producing neurons, the same population of brain cells that gradually dies off in people with Parkinson’s disease. The animals also showed signs of brain inflammation and an abnormal buildup of alpha-synuclein, a protein that clumps together in the brains of Parkinson’s patients and is considered a hallmark of the disease.

Additional experiments in zebrafish helped researchers pinpoint the underlying mechanism. The team found that chlorpyrifos disrupts autophagy, the cellular process responsible for clearing out damaged proteins and cellular debris before they can accumulate and cause harm. When autophagy was disrupted, neurons became significantly more vulnerable to injury. Critically, when researchers either restored the autophagy process or eliminated the synuclein protein in the affected cells, the neurons were protected from the pesticide’s damaging effects, pointing to a specific, targetable pathway rather than a vague or nonspecific form of toxicity.

Outside experts who reviewed the findings said the combination of human and laboratory evidence strengthens the case that chlorpyrifos plays a direct, causal role in some cases of Parkinson’s disease, rather than simply correlating with it. Dr. Michael Okun, a neurologist at the University of Florida and co-author of the book “Ending Parkinson’s Disease,” told The Associated Press that the results help explain the disease’s origins. The findings, he said, provide compelling evidence that this specific pesticide can initiate the biological cascade leading to Parkinson’s.

Nathan Donley, environmental health science director at the Center for Biological Diversity, framed the discovery within a broader pattern of research implicating the chemical in neurological harm, noting that chlorpyrifos has been linked to just about anything that can go wrong in the brain.

Chlorpyrifos is an organophosphate insecticide originally developed by Dow Chemical and introduced in 1965. It has been used for decades on a wide range of crops, including almonds, citrus and cotton. Residential use of the chemical was banned in the United States in 2001, and the U.S. Environmental Protection Agency further restricted its agricultural applications in 2021, but it remains approved for use on close to a dozen crops domestically and continues to be widely used in agriculture in many other countries around the world.

The new findings add to a growing body of research connecting chlorpyrifos exposure to neurological harm across different stages of life. Earlier research has linked the pesticide to impaired brain development and reduced motor function in children exposed during pregnancy or early childhood, building on a string of prior studies examining the chemical’s effects on developing brains. The new UCLA research is among only a handful of studies to specifically investigate chlorpyrifos’s potential role in causing Parkinson’s disease in adults, an area that had previously relied mostly on animal studies showing that the chemical can induce cell death and alter or eliminate neurons, both recognized markers of the disease.

The research arrives amid a broader wave of scientific and legal scrutiny of pesticides and their potential links to Parkinson’s disease. A separate chemical, the herbicide paraquat, has drawn significant attention in recent years after internal corporate documents revealed that Syngenta, the company that manufactures and markets the product, was aware of research linking paraquat to brain disease decades ago. Syngenta now faces thousands of lawsuits from individuals who allege that paraquat exposure caused them to develop Parkinson’s disease, a separate legal and scientific track from the chlorpyrifos findings but part of the same broader push to understand how environmental chemicals may contribute to the disease.

Parkinson’s disease affects nearly 1 million Americans and is characterized by the gradual loss of dopamine-producing neurons in the brain, a process that leads to symptoms including tremors, muscle stiffness, slowed movement and difficulty with balance and coordination. While certain genetic factors are known to raise risk, researchers have increasingly turned their attention to environmental exposures, including pesticides, as important contributors to the disease’s development. There is currently no cure for Parkinson’s, though treatments such as the medication levodopa, along with rehabilitation therapies and, in some cases, surgery, can help manage symptoms and improve quality of life.

The UCLA researchers say their discovery that autophagy dysfunction drives much of the neurotoxicity observed in their experiments points toward a promising new therapeutic target, raising the possibility that future treatments could focus on restoring or boosting the brain’s natural cellular cleanup processes to protect vulnerable neurons. The team also said people with known historical exposure to chlorpyrifos, particularly those who lived or worked near treated agricultural fields for extended periods, might benefit from closer neurological monitoring going forward. Researchers noted that while chlorpyrifos use has declined in the United States in recent years, many people were exposed before current restrictions took effect, and similar organophosphate pesticides remain in widespread use around the world, suggesting the public health relevance of the findings extends well beyond U.S. borders.