Indeed, HMGB1-RAGE/TLR4-NF-κB p65 neuroimmune signaling in neuropathology is associated with AD and AUD (Boissiere et al., 1997; Crews et al., 2013; Vetreno et al., 2013; Fujita et al., 2016; Paudel et al., 2020; Vetreno et al., 2021). This evidence concerns the gene TLR4 and Alzheimer disease.