ABSTRACT
HIV-infected brains are characterized by increased amyloid beta (Aß) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aß homeostasis and contributes to Aß accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aß pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced Aß pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their Aß cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred Aß to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent Aß into the internal carotid artery of mice resulted in Aß fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying Aß can be successfully transferred across the BBB into the brain. Based on these observations, we conclude that HIV-1 facilitates the shedding of brain endothelial ECV carrying Aß; a process that may increase Aß exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain.
