The regular consumption of caffeine/coffee, a non-selective adenosine receptor antagonist that at dose usually consumed by humans (around 200–300 mg caffeine or 3–5 cups of coffee/day) acts particularly as an A2AR antagonist (Fredholm et al., 2005), is inversely correlated with the incidence of AD and later dementia in humans (Maia and de Mendonça, 2002; Eskelinen et al., 2009), and is also protective against cognitive decline in AD mouse models (Arendash et al., 2006; Dall’lgna et al., 2007; Cao et al., 2009; Han et al., 2013; Chen, 2014; Laurent et al., 2014). The gene discussed is ADORA2A; the disease is Alzheimer disease.