MAPT and Alzheimer disease: Thus, it can be hypothesized that H3R antagonist-evoked neurotransmitter release (e.g., ACh) leads to activation of postsynaptic receptor pathways such as phosphorylation-activation of CREB, a transcription factor relevant to cognitive function, and phosphorylation of inhibitory residue Ser9 of GSK3β, a primary tau kinase in AD responsible for tau hyperphosphorylation (Hooper et al., 2008; Bitner et al., 2011).