Receptor for advanced glycation end products (RAGE), an immunoglobulin supergene family member, is also known to be a key molecule in Aβ transcytosis (Yan et al., 2012). Strong staining for RAGE has been reported in the vessels of AD patients (Yan et al., 1996; Donahue et al., 2006) and has been shown to mediate influx of circulating Aβ into brain across the BBB (Deane et al., 2003). In addition, RAGE contributes to Aβ-related synaptic dysfunction and microglial activation (Yan et al., 1996; Origlia et al., 2008, 2010). These findings suggest that RAGE could be a therapeutic target in AD and CAA. Indeed, a RAGE inhibitor ameliorated cerebral Aβ burden and normalized cognitive performance in APP-transgenic mice (Deane et al., 2012). The phase III 18 month clinical trial of the RAGE inhibitor TTP488 is being planned for mild to moderate AD patients (The U.S. National Institutes of Health, 2014); positive results in phase II testing have been reported (Burstein et al., 2014).
