Exposure to Agent Orange damages brain tissue in a way similar to Alzheimer’s disease, study finds

Agent Orange, an herbicide used during the Vietnam War, is a known toxin with numerous health effects. Although Agent Orange has not been used for decades, there is growing interest in its effects on the brain health of aging veterans. A new study led by scientists at Brown University reveals the mechanisms by which Agent Orange affects the brain and how these processes can lead to neurodegenerative diseases.

Research shows that exposure to the herbicidal chemicals from Agent Orange damages brain tissue in the frontal lobe of laboratory rats with molecular and biochemical abnormalities similar to those found in the early stages of Alzheimer’s disease. A first online version of this article detailing the results was published on February 13 and is expected to be published in the Journal of Alzheimer’s Disease.

The findings could have important implications for veterans who were exposed to Agent Orange during the Vietnam War, said study author Dr. Suzanne M. De La Monte, a physician-scientist at the Brown University.

“If we can demonstrate that prior exposure to Agent Orange leads to later neurodegenerative diseases, that gives veterans a chance to get help,” De La Monte said.

But the study results have a much broader significance, she added, because the toxins in Agent Orange are also found in lawn fertilizers.

“These chemicals don’t just affect veterans; they affect our entire population,” said De La Monte, professor of pathology, laboratory medicine and neurosurgery at Brown’s Warren Alpert School of Medicine.

Agent Orange is a synthetic defoliant herbicide widely used between 1965 and 1970 during the Vietnam War. Members of the U.S. military were exposed to the chemical while stationed near aircraft-sprayed enemy territory.

Government reports show that exposure to Agent Orange also caused birth defects and developmental disabilities in babies born to Vietnamese women residing in affected areas. Over time, studies have shown that exposure to Agent Orange is associated with an increased risk of certain cancers as well as cardiovascular disease and diabetes.

Research has also found associations between exposures to Agent Orange and the later development of degenerative diseases of the nervous system, as well as significantly higher rates and earlier onsets of dementia. However, in the absence of a proven causal link between Agent Orange and diseases associated with aging, studies aimed at improving understanding of the process by which the herbicide affects the brain are needed.

“Scientists realized that Agent Orange was a neurotoxin with potential long-term effects, but these have not been clearly demonstrated,” De La Monte said. “That’s what we were able to show with this study.”

The analysis was conducted by De La Monte and Dr. Ming Tong, a research associate in medicine at Brown; both are also associated with Rhode Island Hospital, an affiliate of the Warren Alpert Medical School. Their research builds on their recent studies of exposure to Agent Orange chemicals on immature human central nervous system cells, showing that short-term exposure to Agent Orange has neurotoxic and degenerative effects early onset of Alzheimer’s disease.

Researchers studied the effects of the two main constituents of Agent Orange (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) on markers of Alzheimer’s neurodegeneration using samples from the frontal lobes of laboratory rats. The mature, intact brain tissue samples included a complex array of cell types and tissue structures.

The scientists treated the samples by subjecting them to cumulative exposure to Agent Orange, as well as its distinct chemical constituents, and observed the underlying mechanisms and molecular changes.

They found that treatment with Agent Orange and its constituents caused changes in brain tissue consistent with degeneration of brain cells, as well as molecular and biochemical abnormalities indicative of cytotoxic injury, DNA damage and Other problems.

The approach used by the researchers helped them better characterize the neuropathological, neurotoxic, and neurodegenerative consequences of Agent Orange toxin exposure in young and otherwise healthy brains, as would have been the case for Vietnam War military personnel and many local Vietnam residents.

“Looking for early effects tells us that there is a problem that is going to cause problems later and also gives us an idea of ​​the mechanism by which the agent causes problems,” De La Monte said. “So if you were to intervene, you would know to focus on that early effect, monitor it and try to reverse it.”

Del La Monte hopes to participate in additional research using human brain tissue to evaluate the long-term effects of Agent Orange exposures in relation to aging and progressive neurodegeneration in Vietnam War veterans.

The use of Agent Orange was banned by the U.S. government in 1971. However, the chemicals remain in the environment for decades, De La Monte said. According to the study authors, the widespread and uncontrolled use of Agent Orange in herbicide and pesticide products is such that one in three Americans has biomarker evidence of past exposure.

Despite growing recognition of the broad toxic and carcinogenic effects of 2,4-dichlorophenoxyacetic acid, researchers noted that concern has not reached a sufficient level for federal agencies to ban its use. The researchers conclude that the results of this study and another recent publication support the idea that Agent Orange as well as its independent constituents (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) exert alarming adverse effects on the mature brain. and the central nervous system.

“That’s why it’s so important to look at the effects of these chemicals,” De La Monte said. “They’re in the water; they’re everywhere. We’ve all been exposed.”