Arc-engineered exosomes ease Alzheimer's pathology in animals

In an animal model of Alzheimer's disease, intranasally delivered exosomes engineered with the scaffolding protein Arc alleviated disease symptoms and reduced neuronal damage. The researchers first analyzed 143,214 nuclei using single-nucleus RNA sequencing. This profiling identified excitatory neurons as a primary site of cellular injury, showing marked dysregulation in pathways tied to proteostasis and autophagy. To address these defects, the team engineered neural stem cell-derived exosomes to overexpress Arc. Administered intranasally, the engineered exosomes accumulated in the central nervous system and targeted neurons. In the animals, the therapy reduced β-amyloid deposition, suppressed neuroinflammation, and repaired damaged neurons. Further investigation showed the intervention restored cellular homeostasis by inhibiting mTOR signaling and reactivating autophagy.