TNF and brain disorder: Studies have shown that the levels of TNF-α are significantly elevated in the plasma and cerebrospinal fluid of AD patients (Decourt et al., 2016).In animal models of brain diseases, including AD, upregulation of the PI3K/AKT signaling pathway can inhibit downstream targets such as nuclear factor kappa-B (NF-κB) (Yang et al., 2020), which leads to a reduction in the gene expression and activity of pro-inflammatory cytokines like TNF-α (Bathina et al., 2020).