Widely Used Herbicide Linked to Alzheimer’s-Like Brain Damage

Toxins lurking in our environment may be reshaping our brain health in ways that persist long after exposure ends.

A new study from Arizona State University (ASU), published in the Journal of Neuroinflammation, reveals that glyphosate – the world’s most widely used herbicide – can accelerate Alzheimer’s Disease (AD)-like pathology and cause lasting brain inflammation.

Herbicides and the growing Alzheimer’s population

The increasing prevalence of AD is one of the most alarming public health challenges of our time. More than 6.9 million Americans currently live with this debilitating disorder, a number projected to double to 14 million by 2060. AD devastates lives through memory loss, impaired decision-making and behavioral changes, all driven by complex brain pathologies. These include the build-up of amyloid beta (Aβ) plaques, neurofibrillary tau tangles and chronic neuroinflammation. While genetic predisposition plays a role in some cases, over 95% of AD cases are sporadic, meaning they arise from non-genetic factors. To better understand why such cases arise, researchers are now turning their attention to the environment as a key contributor.

A growing body of evidence links environmental exposure to toxins – through air pollution, poor dietary balance and agricultural chemicals – with the onset of neurodegenerative disease.

“Herbicides are used heavily and ubiquitously around the world,” said co-author Dr. Patrick Pirrotte, an associate professor and director of the Integrated Mass Spectrometry Shared Resource at the Translational Genomics Research Institute (TGen) and City of Hope. 

Among these, glyphosate has come under scrutiny for its potential effects on brain health. In a recent national survey, glyphosate was detected in over 80% of participants. While the U.S. Environmental Protection Agency (EPA) deems it safe for human exposure at current levels, the World Health Organization’s International Agency for Research on Cancer classified it as “possibly carcinogenic to humans” in 2015. Beyond its potential link to cancer, recent research has highlighted glyphosate's effects on other parts of the body, including the brain.

Previous studies have shown that glyphosate can cross the blood-brain barrier, a protective shield that typically prevents harmful substances from entering the brain. Once inside, glyphosate has been detected in brain tissue and linked to elevated levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), which are implicated in neurodegeneration. Glyphosate exposure has also been associated with disruption to processes crucial for learning and memory. Despite these insights, significant gaps remain in understanding glyphosate’s long-term effects on the brain.

“Given the increasing incidence of cognitive decline in the aging population, particularly in rural communities where exposure to glyphosate is more common due to large-scale farming, there is an urgent need for more basic research on the effects of this herbicide,” said corresponding author Dr. Ramon Velazquez, an assistant professor at the ASU.

“Our goal is to identify environmental factors that contribute to the rising prevalence of cognitive decline and neurodegenerative diseases in our society. By unveiling such factors, we can develop strategies to minimize exposures, ultimately improving the quality of life for the growing aging population,” said Velazquez.

Glyphosate’s effects on the brain

The study involved two groups of mice: transgenic mice engineered to develop AD (3xTg-AD) and non-transgenic (NonTg) control mice. The mice were administered glyphosate in daily doses of 0, 50 or 500 mg/kg over a 13-week period. The 500 mg/kg dose corresponded to levels used in previous studies, while the 50 mg/kg dose approximated the threshold considered safe for human exposure according to regulatory standards. This exposure was followed by a six-month recovery period to assess any lasting impacts.

Glyphosate exposure at both 50 mg/kg and 500 mg/kg increased premature death in 3xTg-AD mice, particularly at the lower dose.

Behavioral assessments revealed heightened anxiety-like behavior, indicated by increased thigmotaxia (wall-hugging behavior) in glyphosate-exposed 3xTg-AD mice. However, swim speeds remained consistent across groups, suggesting the behavior change was caused by impaired cognitive performance rather than deficits in motor skills.  

Despite the six-month recovery period, glyphosate's primary metabolite, aminomethylphosphonic acid (AMPA), was detected in the cortical tissues of exposed mice. Glyphosate exposure also led to reduced brain weight in the 50 mg/kg group across genotypes.

Both NonTg and 3xTg-AD mice exhibited elevated levels of peripheral and cortical pro-inflammatory cytokines.

Glyphosate exposure and AD pathology

Glyphosate exposure worsened AD features in the 3xTg-AD mice, demonstrated by an increase in the breakdown products of a key brain protein (amyloid precursor protein, or APP) and higher levels of an enzyme (BACE-1) involved in producing harmful Aβ. Mice exposed to higher glyphosate doses had larger and more abundant Aβ plaques, particularly in the hippocampus, a critical area for memory.

The mice also showed more damage related to tau, another protein linked to AD. Glyphosate exposure led to higher levels of abnormal tau at specific sites and this damage increased with higher glyphosate doses. Staining of brain tissue confirmed more pronounced tau-related damage, especially in neurons in the hippocampus.

Persistent neuroinflammation was also observed in both peripheral blood and brain tissues of glyphosate-exposed mice. The team noted elevated levels of cytokines such as IL-6 and TNF-α, suggesting that even low doses of glyphosate – previously considered safe under regulatory standards – could cause lasting changes in brain health.

A call for stricter regulation on glyphosate use

“Our work contributes to the growing literature highlighting the brain’s vulnerability to glyphosate,” said Velazquez.

Their findings suggest that long-term exposure, even at levels currently deemed safe, could increase the risk of cognitive decline, particularly in aging populations. Given the growing body of evidence, stricter regulations on glyphosate use and residue levels in food may be necessary to mitigate public health risks. The EPA has maintained that glyphosate is minimally absorbed and primarily excreted unchanged. However, this new study challenges those beliefs, by demonstrating the herbicide’s persistent and harmful effects on brain tissue even months after exposure ceases.

“My hope is that our work drives further investigation into the effects of glyphosate exposure, which may lead to a reexamination of its long-term safety and perhaps spark discussion about other prevalent toxins in our environment that may affect the brain,” said first author Samantha Bartholomew, a PhD candidate at ASU.

“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks. However, further research is needed to fully assess the public health impact and identify safer alternatives,” said Pirrotte.

Reference: Bartholomew SK, Winslow W, Sharma R, et al. Glyphosate exposure exacerbates neuroinflammation and Alzheimer’s disease-like pathology despite a 6-month recovery period in mice. J Neuroinflammation. 2024;21(1):316. doi: 10.1186/s12974-024-03290-6

This article is a rework of a press release issued by Arizona State University. Material has been edited for length and content.