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. The gene discussed is PSEN1; the disease is Alzheimer disease.