Nanoplastics exposure exacerbates Aβ plaque deposition in Alzheimer’s disease mice by inducing microglia pyroptosis

Our study addresses the critical issue of environmental relevant dose nanoplastics (NPs) exposure and their neurotoxic effects, highlighting a significant environmental health concern. Using APP/PS1 transgenic mice and BV2 microglial cells, we examined the impact of NPs on cognitive function and Alzheimer's disease (AD) pathology. Our findings reveal that environmental relevant dose NPs exposure aggravated cognitive dysfunction, and exacerbated amyloid-beta (Aβ) plaque formation. NPs cause lysosomal damage and trigger pyroptosis in microglia, impairing their phagocytic function and reducing their ability to clear Aβ plaques. We investigated melatonin as a therapeutic agent, finding it significantly ameliorated cognitive deficits and reduced Aβ plaque deposition, restoring microglial function. This study highlights the significant neurotoxic potential of NPs and suggests targeting pyroptosis as a therapeutic strategy. Our work underscores the urgent need to understand the neurological consequences of NPss exposure and develop strategies to mitigate their health risks.