Microplastics and "Negative Neuroplasticity": An Emerging Topic in Clinical Neurology

Plastics are complex polymeric structures made up of repeating units called “monomers”. The type of monomer subunit determines the material’s strength as well as its commercial function. Most common plastics in daily use are termed “commodity plastics”. These are usually single-use plastics (eg, Styrofoam) made up of polystyrene polymers, used in hot beverage cups and fast food containers. These plastics provide a cost-effective and efficient way to drink, eat, and transport goods, but are poorly recycled, are rapidly discarded as waste, and accumulate rapidly in the environment. These single-use plastics are not as durable as high-performance plastics used in engineering. Therefore, they are prone to more rapid breakdown and fragmentation by the environment. The resulting products of this process are called “microplastics”, which is a generic term that can represent a mixture of many different types of plastics.¹

Microplastics are synthetic particles or polymeric matrices with sizes ranging from 5 mm to 1 μm, which is smaller than the average diameter of a red blood cell (~7-8 μm)^2,2a; therefore, some microplastics are small enough (lipid soluble, <400-600 Daltons) to cross the blood–brain barrier (BBB).^2b,3 Microplastics have been detected in every aspect of the environment, including soil, fresh water, the ocean, the atmosphere, in the Arctic, and on the top of Mount Everest.^1,4-7 Their ubiquitous prevalence within the ecosystem has led to concerns regarding widespread human exposure.⁸

Microplastics have been detected in the placenta, ovaries, testes, kidneys, liver, heart, and brain.^9-13 Their pervasiveness in the environment, as well as evidence from laboratory studies documenting the neurotoxic effects of microplastics in vitro and in animals, along with the observation that microplastics can enter and accumulate in the brain, have raised concerns about their potential role in common neurologic illnesses. Microplastics were found to have accumulated in high concentrations in brains of individuals who died of Alzheimer disease (AD).¹³

We present a concise overview of the current state of knowledge of microplastics and other components of plastics and their effects on the central nervous system, with a focus on dementia, movement disorders, and stroke. We discuss how microplastics enter the brain, accumulate over time, and exert neurotoxic effects as described in case histories and laboratory studies. We also consider practical strategies to reduce plastic exposure and highlight research gaps that must be addressed to clarify how plastic exposure contributes to clinical disease.

Entry and Accumulation of Microplastics in the Brain

Microplastics, like any other toxic compound, can enter the body, localize in tissues, and cause a wide range of effects on human health.¹⁴ Multiple exposure routes have been proposed; however, the current literature suggests the main routes to be inhalation, oral ingestion, and skin contact.⁸ Pathways into the brain could include 3 routes: 1) inhalation, with transport of microplastics through the olfactory nerve (cranial nerve I) down the olfactory pathway; 2) ingestion, with transport through the vagus nerve (cranial nerve X) along the brain–gut axis; and 3) direct crossing through defective areas of the BBB. The Figure shows proposed routes of entry of microplastics into the brain and potential downstream neurotoxic end points. More research is needed to understand how exposure to microplastics contributes to the pathogenesis of neurologic disorders by causing neuroflammation, oxidative stress, blood-brain barrier damage, aggregation of neurotoxic proteins (eg, amyloid-β, alpha-synuclein, tau), and neural cell death.

Figure. Microplastics exposure risk and neurotoxicity. Plastics can fragment into smaller particles, increasing their toxic potential. Microplastics (5 mm to 1 μm) can be inhaled into the nasal epithelium, ingested during eating or drinking, or absorbed into the skin through dermal contact. Microplastics can gain access to the brain through the olfactory nerve, to the vagus nerve through the gut, or by permeating cerebral blood vessels. Created in BioRender. Davis, D. (2025) https://BioRender.com/cj9yb2r

Two recent postmortem studies have provided evidence of the ability of microplastics to enter and accumulate in the brain. A case series evaluating the olfactory bulbs, a region of the olfactory nerve, in 15 decedents with a median age of 69.5 years revealed microplastics in ~50% of the participants.¹⁵ The study identified polypropylene, a polymer used in the manufacturing of food packaging, as the most abundant polymer detected in olfactory tissue. In this study, microplastics ranged from 5.5 to 26.4 μm and varied in polymer composition, including both particles and fibers. A second, more alarming study using archived medical examiner and brain bank biorepository specimens demonstrated that microplastics can accumulate in the brain, their concentrations increased over time, and their presence was severalfold higher in individuals with dementia.¹³ In that study, the most abundant microplastic observed in brain tissues was polyethylene, a polymer used to make the plastic bags used in grocery stores.

Laboratory Evidence of Microplastic Neurotoxicity

Neurotoxic pathways related to microplastics exposure are broad and include oxidative stress, proinflammatory cytokines, altered acetylcholinesterase activity, mitochondrial dysfunction, protein misfolding, disruption of brain homeostasis, and BBB penetration.¹⁷ The broad range of toxic effects is most likely due to the complex chemical nature of microplastics. However, when a single polymer type is examined, direct biologic effects can be delineated. For example, preclinical models have shown that acute exposure to polystyrene microplastics from drinking water leads to decreased expression of astrocyte intermediate fila­ ment glial fibrillary acidic protein.¹⁸ Astrocytes are a crucial component of the BBB, maintaining the homeostasis of neu­rons, and their decreased numbers has been associated with development of neurodegenerative disease.¹⁹

In addition to direct toxic effects, microplastics may also act as carriers or reservoirs for other persistent environmen­ tal pollutants. Microplastics and toxicants can combine to cause additive or synergistic toxicity to the nervous system.

The widespread contamination of microplastics, their broad range of neurotoxic effects, and their potential to combine with other pollutants underscore the complexity and urgent nature of this issue. More research is needed to understand the individual as well as the combined toxic effects of plastic polymer types that make up the composi­tion of microplastics.

Microplastics and Neurologic Disease

AD, the most common form of dementia, is character­ ized by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles.²⁰ As mentioned previously, microplastics have been detected in brain samples from individuals with AD.¹³ Further evidence for a potential role of microplastics in AD comes from a report showing that polystyrene nanoparticles can acceler­ ate the aggregation of Aβ40 and Aβ42 peptides, thereby augmenting their toxicity.²¹ In addition, microplastics can disrupt microtubules, leading to the release of tau proteins.²² Microplastics have also been suggested to directly affect proteins by inducing misfolding and aggregation—processes that can accelerate the pathologic processes involved in the onset of AD.¹⁷

Parkinson disease (PD) is a movement disorder character­ ized by the loss of dopaminergic neurons in the pars compacta region of the substantia nigra. The pathologic hallmark of PD is misfolding and aggregation of the synaptic protein a-synuclein into dense nondegradable structures called Lewy bodies.²³ Nanosized polystyrene plastics can bind to alpha-synuclein, increasing its ability to aggregate.²⁴ In addition, individuals who carry pathogenic variants in LRRK2, which is known to cause PD, may experience increased penetrance when exposed to plastic additives in microplastics (eg, bisphenol-S).²⁵

Cerebrovascular disease—a group of disorders in which the blood vessels in the brain are compromised—most commonly manifests as stroke.²⁶ A recent investigation of people with asymptomatic carotid artery plaques demonstrated that those with microplastics within their plaques had a greater incidence of stroke.²⁷ Patients with risk factors that increased the incidence of stroke, such as vascular calcifica­ tion, had higher concentrations of polypropylene and poly­ styrene microplastics in their fecal matter.²⁸ Microplastics also exert effects on cerebral amyloid angiogenesis and ischemia, given their ability to cause Aβ aggregation and cerebral hemorrhage in model systems.²⁹

Preventative Strategies

Studies are emerging aimed at identifying compounds that can protect against the toxicity of microplastics and eliminate them from the body.^30,31 However, clinical trials to understand the long-term safety and specific responses of these therapies will be difficult to design, because microplas­ tics exposures differ widely.¹⁴ Thus, for the time being, the best approach is to limit exposure to plastics. Reducing per­ sonal exposure can be achieved by making lifestyle changes. Practical guidance that can help mitigate exposure to micro­ plastics from water, food, the home, and the workplace can be found in the Box.

Research Gaps

The precise role of microplastics in neurologic disease is unclear. However, known links between microplastics exposure and common age-related brain diseases highlight a crucial intersection of environmental and neurologic health that requires investigation. The ubiquity of microplastics in the environment, coupled with their demonstrated ability to penetrate the BBB, provide evidence that has thrust experimental neurology into a new era of translational research. A multipronged approach to establishing a research framework is essential to test hypotheses on the toxic effects of microplastics on the brain.

Beyond the bench, scientific inquiry will need to be incorporated with public health initiatives and rapid dissemination of data to policymakers, stakeholders, and lay audiences. Reducing plastic production, improving waste management methods, and using nontoxic alternatives to plastic are essential steps to mitigate exposure to microplastics. In addition, novel technologies must be developed for more sensitive, high-throughput, and cost-effective methods to detect and remove microplastics. Research into potential medical interventions to mitigate neurotoxic effects of microplastics will be more robust once clear mechanisms of toxicity have been established.

Conclusion

As the population ages and plastic production continues to increase, understanding and addressing a connection between microplastics exposure and human health may prove vital in the prevention and management of neurologic diseases. The evolving literature on this topic not only highlights a substantial health concern but also underscores the intricate connections between environmental pollutants and human health.