Neuronal cell cycle re-entry: A doomed journey in Alzheimer disease?

In contrast to fetal brain development, neuronal cells of the adult human brain are terminally differentiated, do not divide and are viewed as being senescent. It is therefore significant that neurons in Alzheimer disease display a phenotype that, in many respects, resembles events related to progression through the cell cycle, leading to the suggestion that these terminally differentiated neurons undergo retro-differentiation to a proliferative state that leads to cytoskeletal alterations and ultimately, cell death. In this review, after summarizing the mitotic alterations in the disease, we discuss how genetic factors of the disease, namely APPP and presenilins, contribute to this doomed journey.