A potential function for neuronal exosomes: Sequestering intracerebral amyloid-β peptide

• Aβ is associated with CSF exosomes of cynomolgus monkeys and APP transgenic mice.
• CSF exosomes decrease age-dependently in APP transgenic mice.
• Neuronal exosomes capture Aβ through their enriched glycosphingolipids.
• Infusion of neuronal exosomes ameliorate Aβ burden in APP transgenic mice.
• These findings highlight the role of neuronal exosomes in Aβ clearance.

Elevated amyloid-β peptide (Aβ) in brain contributes to Alzheimer’s disease (AD) pathogenesis. We demonstrated the presence of exosome-associated Aβ in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated Aβ notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but not glial exosomes, had abundant glycosphingolipids and could capture Aβ. Infusion of neuronal exosomes into brains of APP transgenic mice decreased Aβ and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. These findings highlight the role of neuronal exosomes in Aβ clearance, and suggest that their downregulation might relate to Aβ accumulation and, ultimately, the development of AD pathology.