APP and Alzheimer disease: More than a half of the mutations of the APP family predisposing to AD occur precisely in its transmembrane domain, approximately corresponding either to the residues 700–723 of APP (e.g., V717I/F, A713V, T714I/A, V717F/I/L/G, and L723P in particular), or to the juxtamembrane region 688–694, which is located right after the metal-binding domain in the form of a flexible alpha-helix (e.g., mutations A692G, E693Q/K/G, D694N) [7,19,21,24].