In APP transgenic mice, including PDAPP (Indiana: APP V717F), Tg2576, APPLd2 (London: V642I), APP23 (Swedish), APPSw,Ind (J20), APP/PS1 and 3xTg-AD (APP Swedish, Tau P301L, PS1 M146V), altered hippocampal synaptic plasticity and memory deficits precede amyloid plaque pathology suggesting that disruption of memory neural circuits is independent of plaque deposition (Dodart et al., 1999; Hsia et al., 1999; Koistinaho et al., 2001; Kelly et al., 2003; Van Dam et al., 2003; Dominguez-del-Toro et al., 2004; Billings et al., 2005; Saura et al., 2005; Jacobsen et al., 2006; Gruart et al., 2008). Here, PSEN1 is linked to amyloidosis.