Nanoplastics trigger glial-neuronal collagen signaling miscommunication to exacerbate cognitive impairment in Alzheimer's disease.

Summary

In APP/PS1 mice, 90-day exposure to polystyrene nanoplastics worsened cognition and hippocampal injury while enhancing collagen–integrin-mediated neuroglial signaling. Pharmacologic blockade of integrin (TC-I 15) attenuated collagen activation and rescued cognition, and human single-nucleus RNA-seq confirmed upregulated collagen signaling in AD brains.

Key Findings

• Polystyrene nanoplastics aggravated cognitive deficits and hippocampal damage in APP/PS1 mice after 90-day exposure.
• Proteomics and CellChat analyses showed strengthened collagen–integrin neuroglial signaling, driven by astrocyte/microglia-derived collagen.
• Integrin blockade with TC-I 15 suppressed collagen activation and improved cognition in exposed APP/PS1 mice.
• Human single-nucleus RNA-seq data confirmed upregulated collagen signaling in AD brains.

Clinical Implications

While preclinical, the findings support public health measures to reduce micro/nanoplastic exposure and motivate early-phase trials targeting collagen–integrin signaling in at-risk AD populations.

Limitations

• Exposure model used intragastric polystyrene nanoplastics; real-world human exposures involve mixed polymers, routes, and doses.
• Dose–response and long-term reversibility were not fully characterized; translation to sporadic AD remains to be established.

Future Directions

Define dose–response and exposure mixtures, test additional inhibitors along the collagen–integrin axis, and evaluate biomarkers for human translation in longitudinal cohorts.