Apoptosis decision cascades and neuronal degeneration in Alzheimer's disease.

An important and unique characteristic of neurons is that they are nondividing and irreplaceable. The decisions, then, to engage and execute the apoptotic program are most serious. One of the most surprising new findings in AD brain pathology to date is the large number of neurons affected by DNA damage, even early in the disease process. This may be due to the pressure of chronic apoptotic stressors and the induction of factors which protect the cells from terminal apoptosis. It is possible that Bcl-2, Ref-1, and other such factors may act as apoptotic check points. Thus, there may exist a dynamic and extended competitive decision-making process between cell death processes and compensatory responses in the AD brain, forming a type of neuronal apoptosis decision cascade.