The amyloid cascade hypothesis has been widely accepted as AD etiology. However, our model shows that Aβ accumulation may not be the sole factor in AD etiology. Joint contribution of P-tau and Aβ may be another potential major contributor to the AD progression. Consistent with Prior studies, Aβ toxicity is P-tau dependent (Kayed, 2010; Desikan et al., 2012). In other word, Aβ in the absence of P-tau is not necessarily associated with loss of cognitive function. Previous researches have proposed a possible mechanism for the interaction of P-tau and Aβ. On one hand, P-tau can increase the activity of AChE which can elevate the level of PS-1 and then accelerate the Aβ deposition (García-Ayllón et al., 2011; Silveyra et al., 2012). On the other hand, Aβ can activate tau hyperphosphorylation pathways (García-Ayllón et al., 2011). The crosstalk between Aβ and P-tau forms a vicious cycle in which they elevate each other and trigger cognitive decline.