Of note, ibudilast is currently approved for use as an anti-inflammatory in Japan, improved amyloid beta-induced cognitive impairment in rodent (Wang et al., 2014b) and acts through TLR4 blockade (Schwenkgrub et al., 2017a), reduction of pro-inflammatory cytokines TNF-alpha, IL6 and IL1-beta (Wakita et al., 2003; Schwenkgrub et al., 2017b), up-regulation the anti-inflammatory cytokine IL4 and IL10 and various neurotrophic factors (Mizuno et al., 2004). Here, TLR4 is linked to Cognitive impairment.