Alzheimer’s Disease (AD) is one of the most impacting neurodegenerative diseases worldwide. The current work aims to deep into one of the principal hypotheses investigated in the research to find an effective cure for AD: the Tau hypothesis. According to the Tau hypothesis, Alzheimer’s disease is derived primarily from the hyperphosphorylation of protein MAP Tau, which makes it detach from microtubules, leading to their disruption and so to neuronal death. More in-depth, current research is focusing on the role of temperature and melatonin on the modulation of Tau hyperphosphorylation. Temperature appears as a determining modulator of the activity of kinases and phosphatases, apparently through the modulation of the body's melatonin production and distribution.