TNF and Alzheimer disease: miRNA-21 is downregulated in AD (Juźwik et al., 2019); however, one work has shown that miRNA-21-containing exosomes derived from SH-SY5Y neuroblastoma cells transfected with the Swedish mutant of APP695 (SHSwe), induce microglia M1 polarization, which releases pro-inflammatory cytokines such as high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF)-α, S100 calcium-binding protein B (S100B), and further secretes miRNA-21-containing exosomes, probably as a positive feedback mechanism (Fernandes et al., 2018).