The cell division cycle and the pathophysiology of Alzheimer's disease

Evidence is growing of a role of apoptosis in neurodegenerative disorders including Alzheimer's disease. Recent research indicates that cell cycle disturbances may promote apoptosis in neurodegenerative diseases. In this commentary we will discuss the control of the cell cycle in mammalian cells in general and in the central nervous system in particular. We then summarize the evidence for cell cycle perturbations in Alzheimer's disease and discuss the possible significance these may have for the development of pathological changes in this disease. Our working hypothesis is that, contrary to previous belief, neurons in the adult human brain are capable of re-entering the cell division cycle. The progression of the cell cycle is normally arrested at an early stage and neurons are able to re-differentiate. However, in Alzheimer's disease the cell cycle is allowed to progress into the G2 phase. At this stage re-differentiation is not possible and the neurons will suffer one of two fates: either they will die via an apoptotic pathway or they may produce Alzheimer-type pathology.