APP and Alzheimer disease: In this regard, our findings highlighting a novel mechanistic interplay between APP/Aβ and tau at synapses fit more well with other studies showing that changes in tau metabolism precede Aβ pathology in aged and Alzheimer’s disease brains (Braak and Del Tredici, 2004; Schonheit et al., 2004; Braak et al., 2013; Jack et al., 2013) and that the removal of pathogenetic species of tau can prevent in vivo the deleterious effect of both Aβ and tau (Oddo et al., 2006; Castillo-Carranza et al., 2015; Dai et al., 2017, 2018; Rajamohamedsait et al., 2017).