However, despite rigorous research efforts as reflected by recently completed hundreds of clinical trials, therapeutics targeting two hallmarks of AD, Aβ and tau, have mostly failed so far (Mehta et al., 2017; Congdon and Sigurdsson, 2018; van Dyck, 2018), with few exceptions targeting cholinergic and glutamatergic pathways that provide only symptomatic relief for a short time, indicating that novel pathways and molecular targets must be identified to bring disease-modifying therapy for AD. Here, MAPT is linked to Alzheimer disease.