The amino-terminal projection domain of human tau—which interacts with the plasma membrane (Brandt et al., 1995) and undergoes early conformational changes in human tauopathies including Alzheimer’s disease (Combs et al., 2016, 2017)—is endowed with deleterious action(s), mainly at nerve endings (King et al., 2006; Ittner et al., 2010; Amadoro et al., 2012; Zhou et al., 2017). The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.