Contribution of iron to neurodegeneration in AD has also been proposed to occur based on its ability to influence four pathways implicated in AD: (1) APP metabolism (Mantyh et al., 1993; Bodovitz et al., 1995; Schubert and Chevion, 1995; Rottkamp et al., 2001; Rogers et al., 2002; Kuperstein and Yavin, 2003), (2), the loss of calcium homeostasis (Hidalgo and Nunez, 2007), (3) the degradation of a subset of microglia (Lopes et al., 2008), and (4) oxidative stress (Honda et al., 2004; Liu et al., 2006; Smith, 2006; Castellani et al., 2007, 2012). Here, APP is linked to Alzheimer disease.