For instance, studies in adult AIE-treated rats as well as in human AUD and AD studies report reductions of basal forebrain cholinergic neurons and increased expression of proinflammatory Toll-like receptor 4 (TLR4), receptor for advanced glycation end-products (RAGE), and the endogenous TLR4/RAGE cytokine-like agonist high-mobility group box 1 (HMGB1) (Arendt et al., 1983; Vetreno et al., 2014; Heneka et al., 2015; Crews et al., 2019; Paudel et al., 2020; Vetreno et al., 2021). This evidence concerns the gene TLR4 and Alzheimer disease.