Nanoplastics forming micro-sized agglomerates and exacerbating neurotoxicity in Alzheimer's disease

Micro/nanoplastics are quietly infiltrating human bodies through dietary intake, water consumption, and dermal exposure. Here, we assessed the interaction of nanoplastics (NPs) with β-amyloid (Aβ), helping to understand the likely mechanisms of NPs accumulation in brain and potential impacts on Alzheimer's disease (AD). SH-SY5Y cells served as an in vitro model of AD and were treated with fluorescently labeled NPs (NPf). In in vivo study, 5XFAD mice were fed with environmentally relevant doses of NPf for two weeks, and mouse behavior was analyzed by open field test. Brain tissue sections combined with confocal microscopy enabled the quantification and spatial localization of NPf in the brain. NPs aggregated with Aβ fibers and formed micrometer-sized agglomerates. In AD cell models, these agglomerates increased the intracellular NPs accumulation, reactive oxygen species formation and ethoxyresorufin-O-deethylase activity, ultimately inhibiting neurite outgrowth and causing cell death. In the AD mice, NPs exposure worsened the mice disease-related behaviors (e.g., reduced movement distance and speed) and resulted in larger NPs agglomerates and highly co-localization with Aβ in brain, consistent with the in vitro results. This study provided important data on NPs interaction with Aβ fiber from ex vivo to in vivo models, helping to understand the mechanisms of NPs accumulation in the brain.