Given the fundamental importance of NE signaling to the enhancement of PC synaptic plasticity (Morrison et al., 2013; Ghosh et al., 2017a), odor valence and discrimination (Shakhawat et al., 2015; Ghosh et al., 2021), it is plausible that the early stages of soluble pretangle tau initially expressed within the LC could directly influence olfactory dysfunction observed in preclinical AD. This evidence concerns the gene MAPT and Alzheimer disease.