Exosomes derived from olfactory mucosa mesenchymal stem cells attenuate cognitive impairment in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and endoplasmic reticulum (ER) stress. In recent years, exosomes have garnered significant attention as a potential therapeutic tool for neurodegenerative diseases. This study, for the first time, investigates the neuroprotective effects of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exos) in AD and further explore the potential role of low-density lipoprotein receptor-related protein 1 (LRP1) in this process. Using an Aβ1-42-induced AD mouse model, we observed that OM-MSCs-Exos significantly improved cognitive function in behavioral tests, reduced neuroinflammatory responses, alleviated ER stress, and decreased neuronal apoptosis. Further analysis revealed that OM-MSCs-Exos exert neuroprotective effects by modulating the activation of microglia and astrocytes and influencing the ER stress response, a process that may involve LRP1. Although these findings support the potential neuroprotective effects of OM-MSCs-Exos, further studies are required to explore their long-term stability, dose dependency, and immunogenicity to assess their feasibility for clinical applications.