TNF and Cognitive impairment: Cognitive deficits and AD-related cognitive decline in DS individuals are associated with neuroinflammation (Caraci et al., 2017), a deficit of neurotrophic factors (Hartley et al., 2015; Iulita et al., 2016a) and an “inflammatory endophenotype” (Ahmed et al., 2021) with increased concentrations of pro-inflammatory cytokines (e.g., IL-1 and TNF-α) (Iulita et al., 2016b).