THE CELL-DIVISION CYCLE AND THE PATHOPHYSIOLOGY OF ALZHEIMERS-DISEASE

Evidence is growing of a role of apoptosis in neurodegenerative disord ers including Alzheimer's disease. Recent research indicates that cell cycle disturbances may promote apoptosis in neurodegenerative disease s. In this commentary we will discuss the control of the cell cycle in mammalian cells in general and in the central nervous system in parti cular. We then summarize the evidence for cell cycle perturbations in Alzheimer's disease and discuss the possible significance these may ha ve for the development of pathological changes in this disease. Our wo rking 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 sta ge and neurons are able to re-differentiate. However, in Alzheimer's d isease the cell cycle is allowed to progress into the G(2) phase. At t his stage re-differentiation is not possible and the neurons will suff er one of two fates: either they will die via an apoptotic pathway or they may produce Alzheimer-type pathology. (C) 1998 IBRO. Published by Elsevier Science Ltd.