DR confers protection against excitotoxic damage in mouse neurons expressing a familial AD mutation in presenilin-1 (Zhu et al., 1999), reduces Aβ deposition (Patel et al., 2005; Wang et al., 2005; Halagappa et al., 2007), reduces tau hyperphosphorylation (Halagappa et al., 2007; Wu et al., 2008) and improves cognitive dysfunction in mouse models of AD (Halagappa et al., 2007). This evidence concerns the gene PSEN1 and Alzheimer disease.