The age-related neurodegenerative diseases drew the interest of the scientific community, due to the gradual increase of the average age in the World’s population. Recent studies indicated the altered cell cycle in the triggering of neurodegenerative diseases such as Alzheimer’s disease (AD). This process seems to involve the nuclear tau, a protein which we previously shown to have a central role in the neuronal in vitro differentiation. In this work, we studied the role of the nuclear tau protein, specifically of the AT8 epitope, in the onset of AD, to evaluate its possible use as an early molecular marker. The immunolocalization in neurons of CA1 region of the human hippocampus from normal, senile and AD subjects, shown that AT8 epitope decreases in senile neurons respect to youngers, indicating its possible role in the ectopic activation of the cell cycle in differentiated cells. Here we show data that improve the knowledge on the role of nuclear tau in neuronal differentiation and cell degeneration in AD, involving the presence/absence of AT8 in the nucleolus of neurons related to a re-entering in the cell cycle. The molecular mechanisms related to the start of AD are not yet clear, so their understanding is very relevant if we consider the social impact of this disease in the human populations.