In Alzheimer’s disease, highly phosphorylated tau is mislocalized to synaptic compartments (Perez-Nievas et al., 2013) where tau disrupts synapse function and mediates synaptotoxicity (Ittner et al., 2010; Li and Gotz, 2017; Zhou et al., 2017; McInnes et al., 2018). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.