As well as binding AGEs, RAGE is also activated by calgranulins (Hofmann et al., 1999), amyloid-beta (Aβ) peptides (Yan et al., 1996; Takuma et al., 2009; Piras et al., 2016), associated with Alzheimer’s disease, and high-mobility group protein 1 (HMGB1) (Huebener et al., 2015), a chromatin protein which functions in the nucleus, but is released by immune cells as a leaderless cytokine (Klune et al., 2008). This evidence concerns the gene AGER and Alzheimer disease.