Cerebral to SystemicRepresentations of Alzheimer’sPathogenesis Stimulated by Polystyrene Nanoplastics

Plastics discharged into the ecosphere can transform into micro- and nanoparticles to instigate interactions with biosystems, posing a threat to environmental sustainability and human health. While nanoplastics have recently been identified in abundance in the human brain, especially in the decedent brain tissues of dementia subjects, how these exogenous miniatures mediate neurological as well as systemic pathologies remains unclear. Here, we first investigated how environmental-level nanoplastic exposure influences the progression of Alzheimer’s disease, from cerebral to systemic representations. Specifically, polystyrene nanoplastics aggravated Alzheimer’s-like symptoms in both wild-type and APP/PS1 mice and stimulated microglial activation and hippocampal neuronal death, accentuated by peripheral abnormalities of lipid accumulation, hepatic steatosis, inflammation, adipocyte enlargement, and gut microbiota imbalance. These findings implicate that nanoplastic-induced neurological damage is not confined within the brain but expands systemically through the gut–liver–brain axis, thereby contributing to the multiscale and multidirectional progression of Alzheimer’s pathophysiology.