Abstract
Understanding the neurological impact of nanoplastic exposure has become an area of intensive research recently. This study examined the molecular and cellular mechanisms of how nanoplastics affect amyloid-beta (Aβ) clearance by microglia in the context of Alzheimer's disease (AD). Transmission electron microscopy and molecular dynamics simulations showed that polystyrene nanoplastics accelerated Aβ aggregation by forming a protein corona, promoting peptide fibrillization through hydrogen bonding and π-π interactions. Flow cytometry and endocytosis inhibition assays revealed that polystyrene nanoplastics impaired microglial uptake of Aβ while increasing their own cellular internalization, leading to microglial energy depletion and allowing Aβ aggregates to evade immune clearance. Additionally, proteomic analysis indicated that polystyrene nanoplastics disrupted microglial homeostasis, exacerbated neuroinflammation and metabolic dysregulation, and impaired the signalling pathway of ABC transporters critical for Aβ clearance in the AD brain. These findings suggest that nanoplastics contribute to AD pathology by impeding Aβ clearance and corrupting neuroimmune defense.