Remarkably, using amyloidogenesis AD mouse models, it was shown that the genetic ablation of a myriad of putative Aβ signaling downstream players, such as tau2, PrP3, GIVA-phospholipase A2 (GIVA-PLA2)4 or phospholipase D2 (PLD2)5 ameliorates rodent behavioral cognitive deficits, independently of APP processing or Aβ levels modulation. The gene discussed is APP; the disease is Alzheimer disease.