Chronic polystyrene microplastic exposure worsens cognitive dysfunction and Alzheimer's Disease-like neuropathology in APP/PS1 mice.

Microplastics are emerging environmental contaminants with potential neurotoxic effects, but their impact on Alzheimer's disease (AD)-susceptible brains remains unclear. This study examined whether chronic exposure to 1 μm polystyrene microplastics (PS-MPs) aggravates cognitive dysfunction and AD-like neuropathological injury in APP/PS1 mice. Four-week-old male APP/PS1 and C57BL/6 mice were exposed to fluorescent PS-MPs at 100 μg/L in drinking water for six months. Spatial learning and memory were evaluated using the Morris water maze. Brain fluorescence signals, neuronal injury, amyloid-reactive staining, glial activation, DNA fragmentation-associated injury, and cGAS-STING pathway markers were examined by in vivo imaging, histology, immunofluorescence, and Western blotting. PS-MPs exposure was associated with enhanced brain-region fluorescence signals and mild pathological changes in C57BL/6 mice. In APP/PS1 mice, PS-MPs exposure further prolonged escape latency, reduced platform crossings and target-quadrant residence time, increased amyloid-reactive staining, decreased NeuN signals, enhanced Iba1 and GFAP immunoreactivity, increased TUNEL-positive signals, and increased cGAS, STING, TBK1, and p-IRF3/IRF3. These findings suggest that chronic PS-MPs exposure aggravates AD-like cognitive and neuropathological abnormalities in APP/PS1 mice and is accompanied by cGAS-STING-related inflammatory signaling.