APP and Alzheimer disease: For AD models we used the hTau transgenic model of age-related tauopathy (mice expressing all six isoforms of human tau, on a null murine tau background) and the PSAPP mouse model of amyloid pathologies [carrying the PS1(M146L), and APP(K670N, M671L) mutations], in which emerging neurological and histopathological features have been well characterized (Holcomb et al., 1998; Duff et al., 2000; Arendash et al., 2001; Gordon et al., 2002; Andorfer et al., 2003, 2005; Sadowski et al., 2004; Trinchese et al., 2004; Polydoro et al., 2009).