These hypotheses include: (1) amyloid hypothesis, which posits that the gene mutations of APP and PS1/2 induce the overexpression or deficient removal of Aβ toxic species, and thus lead to the other two cardinal changes associated with AD (Figure 1); (2) tau hypothesis, which believes that the hyperphosphorylated tau protein disassembles from microtubules and subsequently induces neuronal death (Figure 1); (3) unknown triggering hypothesis, which postulates that some uncertain factors lead to the neurodegeneration, both directly and indirectly, through the formation of plaques and tangles. This evidence concerns the gene APP and Alzheimer disease.