MAPT and early-onset autosomal dominant Alzheimer disease: Although tau and amyloid-β have complex and synergistic effects (Nisbet et al., 2015), there is converging evidence that tau mediates direct toxic effects on neurons and synaptic plasticity (Ballatore et al., 2007; Roberson et al., 2007; Ittner and Götz, 2011; Myeku et al., 2016) and correlates with hypometabolism and symptomatology in Alzheimer’s disease (Lehmann et al., 2013; Ossenkoppele et al., 2015, 2016).