Accumulating evidence have suggested that the detrimental effects of Aβ are dependent on tau pathology (Rapoport et al., 2002; King et al., 2006; Roberson et al., 2007; Ittner et al., 2010; Vossel et al., 2010; Desikan et al., 2011; Shipton et al., 2011; Nussbaum et al., 2012; Bloom, 2014) and that tau, rather than Aβ (Murray et al., 2015), serves a prominent role in early synaptic decline and cognitive impairment (Arriagada et al., 1992; Ashe and Zahs, 2010; Nelson et al., 2012; Pontecorvo et al., 2017; Busche et al., 2019). The gene discussed is MAPT; the disease is Cognitive impairment.