APP and Alzheimer disease: Different animal models have been analyzed to decipher the role of RAGE in AD progression: (i) injection of AGEs into the rat hippocampus; (ii) injection of Aβ in rat hippocampus; (iii) various transgenic (Tg) mice expressing one or more gene variant of the amyloid precursor protein (APP); (iv) presenilins, which are implicated in APP cleavage and Aβ production leading to amyloid plaque formation; (v) tau that forms the characteristic tangles when is hyperphosphorylated.