The “X” model of AD progression proposes that MCI patients who finally convert to AD exhibit a significant disruption (i.e., decrease in synchronization; König et al., 2005; López-Sanz et al., 2017; Pusil, Dimitriadis, et al., 2019) between anterior cingulate cortex (ACC) and precuneus (PC), two default mode network (DMN) hubs typically involved in the spreading of amyloid beta (Forsberg et al., 2008; Hampel et al., 2021; Sepulcre et al., 2018) and tau (Hampel et al., 2021; Tekin et al., 2001) in the human cortex. The gene discussed is MAPT; the disease is Alzheimer disease.