Scientists have demonstrated that short-term exposure to microplastics causes Alzheimer’s-like effects in mice expressing human APOE4 versus APOE3. These effects were sex-dependent, mirroring the disease in humans [1].
Microplastics and the brain
Exposure to tiny particles that plastic products shed (microplastics) has been linked to increased mortality and diseases [2]. Microplastics are ubiquitous and enter organs, including the brain, triggering inflammation. A recent study showed alarming levels of microplastic accumulation in human brains [3]. However, rigorous studies of the exact effects of microplastics on the brain have been scarce.
A new study by researchers at the University of Rhode Island College of Pharmacy asked a question whether microplastics exposure can promote Alzheimer’s disease in mice genetically predisposed to it. The team created genetically modified mice that were homozygous for either the human APOE ε3 or APOE ε4 allele. The latter is strongly associated with an increased risk of Alzheimer’s, while the former is considered “normal,” neither increasing risk nor providing protection. Both sexes were included to avoid missing sex-specific effects.
At 3-6 months of age, before developing pathologies, mice were randomized into control or exposure groups, with 8 animals per each combination of sex, genotype, and condition. Then, for three weeks, the treatment groups drank water containing a mix of fluorescent polystyrene particles at two sizes: 0.1 μm (nanoplastic) and 2 μm (microplastic), at 0.125 mg/mL. The chosen dose was intentionally high relative to what the average human receives from the environment. This was done to compensate for the short duration of exposure.
“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 URI pharmacy assistant professor Jaime Ross, the lead author of the study.
Males more apathetic, females more forgetful
The team then ran a battery of cognitive tests. In the open field test, cognitively normal mice are expected to spend little time in the open, which is these rodents’ natural behavior helping them to avoid predators. Male APOE ε4 mice who were exposed to microplastics, however, spent much more time in the center of the arena, a pattern that the authors interpret as apathy-like cognitive disruption.
Females did not show this pattern. However, in a different test, novel object recognition (NOR), it was the female APOE ε4 mice who showed poorer recognition memory. Several other tests produced null results, but the authors suggest it actually shows that, just like in human Alzheimer’s, the effect was less “broad anxiety” and more cognition-focused.
Ross tied the findings to known sex-related differences in Alzheimer’s symptoms in humans. “In human Alzheimer’s patients,” she said, “men tend to experience more changes in apathy; they care less. Women experience more changes in memory. So, the memory and the apathy connection are pretty clear: when you expose animals that are carrying the largest known risk factor in humans for developing Alzheimer’s disease to micro- and nanoplastics, lo and behold, their behavior changes in a sex-dependent manner similar to the sex-dependent differences we see with Alzheimer’s patients.”
“Similar to what we’re seeing in the real world”
The plastic particles were confirmed to reach the brain, at least the larger ones (0.1 μm particles are below histology detection limits), and the researchers attempted to analyze possible mechanisms behind the impact on cognition. The team examined GFAP, a marker of astrocyte activation/health, and IBA1, a microglial marker, but the results were inconclusive. The researchers suggest that microplastics exert their effect on cognition not via classical microglial inflammation and call for further research.
Two important caveats apply. First, the high dose and short exposure limits the study’s generalizability. Second, real-world plastics are weathered, chemically varied, and often carry adsorbed pollutants. This study used pristine polystyrene spheres, which do not mirror these conditions.
“So, that tells us there’s something about lifestyle, something about the environment going on,” Ross said. “There are modifiable factors we’re studying related to Alzheimer’s – diet, exercise, vitamins, and especially environmental toxins like microplastics. If you carry the APOE4, and you happen to consume a lot of microplastics, will this contribute to Alzheimer’s disease?”
“There has not been a lot of money spent on the human health impacts of microplastics,” she added. “It’s interesting that what we’re seeing in mice is similar to what we’re seeing in the real world. We want to encourage further research into the scourge of micro- and nanoplastics.”
Literature
[1] Gaspar, L., Bartman, S., Tobias-Wallingford, H., Coppotelli, G., & Ross, J. M. (2025). Short-term exposure to polystyrene microplastics alters cognition, immune, and metabolic markers in an apolipoprotein E (APOE) genotype and sex-dependent manner. Environmental Research Communications, 7(8), 085012.
[2] Marfella, R., Prattichizzo, F., Sardu, C., Fulgenzi, G., Graciotti, L., Spadoni, T., … & Paolisso, G. (2024). Microplastics and nanoplastics in atheromas and cardiovascular events. New England Journal of Medicine, 390(10), 900-910.
[3] Nihart, A. J., Garcia, M. A., El Hayek, E., Liu, R., Olewine, M., Kingston, J. D., … & Campen, M. J. (2025). Bioaccumulation of microplastics in decedent human brains. Nature medicine, 31(4), 1114-1119.
View the article at lifespan.io
