Microplastics Cause Cognitive Deficits in APOE4 Mice

by September 12, 2025

Scientists have demonstrated that exposure to microplastics significantly impacts cognitively sensitive mouse models that carry the Alzheimer’s-promoting allele APOE4. The study findings reveal notable disparities in effects based on sex, with male mice exhibiting symptoms of apathy and female mice showing signs of memory loss.

Microplastics and the Brain

Microplastics, tiny particles that shed from plastic products, have been shown to have detrimental effects on health, including increased mortality rates and various diseases (Marfella et al., 2024). Recent studies have alerted us to alarming levels of microplastic accumulation in human brains (Nihart et al., 2025). However, rigorous examinations on the exact effects of these particles on brain function remain limited.

A research team at the University of Rhode Island College of Pharmacy investigated whether microplastic exposure could exacerbate Alzheimer’s disease in genetically predisposed mice. They engineered mice to be homozygous for either the APOE ε3 or APOE ε4 allele. While the former is regarded as “normal,” the latter correlates strongly with increased risk of Alzheimer’s disease. Importantly, the study included both male and female subjects to avoid overlooking potential sex-specific effects.

At the age of 3-6 months, before any neurological pathologies could manifest, the mice were assigned to control or exposure groups, ensuring there were eight animals for each sex, genotype, and condition. The treatment groups were subjected to drinking water containing a mixture of fluorescent polystyrene particles at two distinct sizes: 0.1 μm (nanoplastic) and 2 μm (microplastic), at a concentration of 0.125 mg/mL. This elevated dose was intentionally high, relative to what an average human might encounter in their environment, thus compensating for the limited exposure duration of the study.

"In these mice, like in people, it’s not a guarantee that you’re going to see any changes in cognition. You could have identical twins both carrying APOE4, one totally cognitively healthy, and the other could develop Alzheimer’s disease," said Jaime Ross, the lead author of the study.

Males More Apathetic, Females More Forgetful

The research team conducted a series of cognitive assessments. During the open field test, cognitively healthy mice are expected to limit their time in open spaces—a behavior that aids in evading potential predators. The results indicated that male APOE ε4 mice exposed to microplastics spent significantly more time in the center of the arena, an observation the researchers interpreted as apathy-like cognitive disruption.

In contrast to male mice, female APOE ε4 mice did not display the same apathy pattern. Instead, when subjected to a different cognitive assessment, the novel object recognition (NOR) test, it was specifically the female APOE ε4 mice that displayed poorer recognition memory. While additional tests yielded inconclusive results, the authors posited that this indicated a focus on cognition rather than generalized anxiety, akin to patterns observed in human cases of Alzheimer’s disease.

Ross correlated these experimental findings with known sex-related variations in Alzheimer’s symptoms observed in humans. "In human Alzheimer’s patients,” she noted, “men tend to suffer more from apathy; they care less. Females are more affected by memory changes. Thus, the connection between memory and apathy is evident.”

Mechanisms of Cognitive Disruption

Post-exposure, the analysis confirmed that microplastics indeed reached the brain, particularly with larger particles (0.1 μm), which dictated histological detection limits. The research team also scrutinized two markers: GFAP, indicating astrocyte activation or health, and IBA1, a microglial marker. The results of these examinations were inconclusive, leading researchers to speculate that the cognitive effects of microplastics occur through means other than traditional microglial inflammation.

However, two significant caveats must be highlighted. First, the high dosage and limited exposure duration may restrict the study’s broader applicability. Second, real-world plastic products are often weathered, chemically diverse, and can carry various pollutants, whereas the study exclusively used pristine polystyrene spheres, which do not accurately represent common environmental plastics.

"This suggests there’s something about lifestyle, something about the environment at play," Ross claimed. "We are exploring modifiable factors related to Alzheimer’s – diet, exercise, vitamins, and especially environmental toxins like microplastics. If you possess the APOE4 risk allele and consume significant amounts of microplastics, could this contribute to Alzheimer’s disease?"

Call for Further Research

Ross lamented the scant funding allocated to studying the implications of microplastics on human health. "What we observe in mice parallels what is becoming evident in our daily lives. We hope to stimulate further investigation into the significant implications of micro- and nanoplastics."

Literature

This study highlights the urgent need for enhanced research funding to fully understand the complex consequences of microplastics on health, notably cognitive health in genetically predisposed populations.

Author: Arkadi, a seasoned journalist passionate about the intersection of health, science, and longevity.