APP and Alzheimer disease: For example, the 3xtg-AD mouse model was generated by expressing human tau with P301L mutation combined with an APP transgene with Swedish mutation expressed in a PSEN1 knock-in mouse.34,43 In another model, a cross-breed between the APP transgenic Tg2576 and JNPL3 mouse models, the injection of a long form of Aβ42, induces NFT formation and tau phosphorylation in areas projecting to the injection site.34,44 Findings from such combinatorial models have made clear the interaction between tau and Aβ, although it is not entirely clear which protein (tau or Aβ) is downstream of the other.