MAPT and early-onset autosomal dominant Alzheimer disease: However, albeit tau appears to be the main factor underlying the development and progression of Alzheimer’s disease (Kametani and Hasegawa et al., 2018; Castellani and Perry, 2019), its expression at physiological level is required for neuronal functions underlying learning and memory (Pooler et al., 2014; Regan et al., 2017) and its down-regulation, even if moderate, has been proved to have deleterious effects, both in vitro and in vivo (Biundo et al., 2018; Velazquez et al., 2018).