As a proof of concept of such a hypothesis, human post-mortem studies had shown that the hypothalamus suffers from a relevant burden of tau-pathology in AD, especially considering the nuclei involved in the regulation of circadian rhythm and the sleep/wake cycle (see “Circadian rhythm and sleep/wake cycle: potential role of LC-hypothalamic interactions” section), such as the already mentioned TMN, but also the SCN, the dorsomedial nucleus (DMN) and the ventromedial nucleus (VMN) (Hiller and Ishii 2018). This evidence concerns the gene MAPT and Alzheimer disease.