Hypoxia increases amyloid-β level in exosomes by enhancing the interaction between CD147 and Hook1.

Hypoxia promotes the accumulation of amyloid-β (Aβ), which is related to the pathogenesis of Alzheimer's disease (AD). CD147 is considered as an additional subunit of γ-secretase regulated by hypoxia, and has been identified in exosomes. Aβ is also found in exosomes that participate in the intercellular communication and amyloids propagation. This study was to investigate the role of CD147 in hypoxia-induced accumulation of Aβ in exosomes. Our results showed that hypoxia increased the levels of Aβ40 and Aβ42 in exosomes and enhanced the interaction between CD147 and Hook1 in SH-SY5YAPP695 cells. Moreover, hypoxia increased the interaction between amyloid precursor protein (APP) and CD147 as well as the expression of CD147 in isolated membrane. After we interfered the interaction between CD147 and Hook1 by decreasing Rab22a expression, the hypoxia induced Aβ accumulation in exosomes was significantly suppressed. In addition, the increased interaction between CD147 and Hook1 was further confirmed in hypoxia exposed C57BL/6 mice. Our findings reveal that hypoxia may increase exosome Aβ level by enhancing the interaction between CD147 and Hook1.