APP and early-onset autosomal dominant Alzheimer disease: At the experimental level, long-term caffeine treatment has been demonstrated to ameliorate cognitive impairment in animal models of Alzheimer disease: βA-injection mouse models (Dall’Igna et al., 2007; Canas et al., 2009) and transgenic mouse models including APP (Arendash et al., 2006; Cao et al., 2009; Chu et al., 2012), APP/PS1 (Cao et al., 2011; Han et al., 2013), and more recently in a tau transgenic model (Laurent et al., 2014).