Extracellular vesicles of the blood-brain barrier: Role in the HIV-1 associated amyloid beta pathology

HIV-infected brains are characterized by increased amyloid beta (A beta) deposition. It is believed that the blood brain barrier (BBB) is critical for A beta homeostasis and contributes to A beta accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in A beta 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 A beta pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their Ala cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred A beta to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent A beta into the internal carotid artery of mice resulted in A beta fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying A beta 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 A beta; a process that may increase Pip exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain. (c) 2017 Elsevier Inc. All rights reserved.