This may accord with activity-dependent accumulation of tau and Aβ where hyperactivity as a result of Aβ in the early stage Alzheimer’s disease might be involved in faster spreading of tau across networks and consequently more damage to the functional connections.34,46-48 Furthermore, it is hypothesized that Aβ might remotely and locally increase tau spreading and further accelerate functional disconnection.49 Together, the current study provides a better view of the spatial effect of tau pathology and the mediating role of Aβ on FC and then cognitive impairment. Here, MAPT is linked to Alzheimer disease.