Both the BV2 and primary microglial cells derived-MDEVs were demonstrated to carry the NLRP3 and IL1β cargoes that, upon being uptaken by the neurons, resulted in synaptodendritic injury and lowering excitatory postsynaptic currents, suggesting that the MDEVs via an NLRP3 dependent mechanism could be a contributing factor for HAND pathogenesis. Here, NLRP3 is linked to HIV-associated neurocognitive disorder.