Concerning the earlier appearance of Aβ in this 3xTg-AD mouse model, our findings provide some support for the amyloid cascade hypothesis which predicts that Aβ is the initiating trigger of cascade reaction of subsequent pathological changes that underlies AD (Hardy and Selkoe, 2002) and that the accumulation of p-Tau is driven by amyloid pathology (Karran and De Strooper, 2016). Here, MAPT is linked to Alzheimer disease.