APOE and Alzheimer disease: Given the view that pDMN vulnerability to Aβ accumulation is linked to its role as a large-scale connectivity hub (Jagust and Mormino, 2012, Jones et al., 2016), heightened pDMN activity in young APOE-ε4 carriers may itself be linked to variation in structural connectivity (Brown et al., 2011, de Haan et al., 2012), particularly with other regions affected early in AD.