MAPT and early-onset autosomal dominant Alzheimer disease: Independently of its ability of seeding aggregation, abnormal extracellular/intracellular tau is per se neurotoxic (Diaz-Hernandez et al., 2010; Medina and Avila, 2014a, b; Hu et al., 2018) and propagates trans-synaptically along interconnected neuronal networks in a stereotypical manner which strongly correlates with the development of clinical symptoms during Alzheimer’s disease progression (Mohamed et al., 2013; Pooler et al., 2013; Yamada et al., 2017).