Mitochondrial cascade hypothesis of Alzheimer's disease: myth or reality?

Mitochondria are recognized to play a pivotal role in neuronal cell survival or death because they are regulators of both energy metabolism and apoptotic pathways. Morphologic, biochemical, and molecular genetic studies suggest that mitochondria might be a convergence point for neurodegeneration, including Alzheimer's disease (AD). The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress. However, the question, "Is mitochondrial dysfunction a necessary step in neurodegeneration?" is still unanswered. This review presents the ways in which malfunctioning mitochondria and oxidative stress might contribute to neuronal death in AD.