Microplastics as Emerging Neurotoxins: Brain Accumulation, Neuroinflammation, and Neurodegeneration Risk

ABSTRACT Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants with profound implications for human neurological health. Recent landmark findings confirm the bioaccumulation of MPs/NPs in human brain tissue—with concentrations reaching 4917 μg/g in 2024 autopsy samples and up to 10‐fold higher levels in individuals with dementia—underscoring the urgent need for mechanistic understanding. This review synthesizes current evidence on the routes by which MPs/NPs traverse the blood‐brain barrier (BBB) and the olfactory pathway, their cellular effects within the central nervous system (CNS), and the molecular cascades that link plastic particle exposure to neuroinflammation and neurodegeneration. Key mechanisms include: disruption of tight junction proteins and BBB integrity; activation of microglia and the NLRP3 inflammasome; induction of oxidative stress via reactive oxygen species (ROS); mitochondrial dysfunction through impairment of the electron transport chain; synaptic toxicity and neurotransmitter dysregulation; and direct promotion of pathological protein aggregation—including amyloid‐beta (Aβ), tau hyperphosphorylation, and α‐synuclein fibrillation—implicated in Alzheimer's disease (AD) and Parkinson's disease (PD). Indirect neurotoxicity via the gut‐brain axis is also addressed. Finally, critical research gaps and future directions are proposed, including standardized exposure models, longitudinal human cohort studies, and evaluation of therapeutic targets. This review positions MPs/NPs as a novel environmental risk factor for neurodegenerative diseases warranting priority attention in neuroscience and public health research.