Energy Metabolism, Oxidative Stress and Neuronal Degeneration in Alzheimer's Disease

Both altered energy metabolism and oxidative stress have been proposed to contribute to tissue damage in neurogenerative diseases. Animal models and cell culture studies provide evidence for a role of these processes in several forms of neuronal death. Reductions in the activities of some key mitochondrial enzymes have been found in autopsied brain in Alzheimer's disease. However, results obtained with biopsied brain tissue as well as assessments of metabolic rates for glucosein vivoindicate that a reduced functional capacity of mitochondria is probably not a general feature in the brain in Alzheimer's disease. These studies do not address the possibility that short-lived changes in energy metabolism affecting a small number of cells at any one time could be contributing to cell death. Several findings point to a moderate increase in oxidative damage in those areas of brain which are most severely affected in this disease, probably resulting from an increase in production of reactive oxygen species. Whether this is a contributor to neurodegeneration or a consequence of it remains unresolved.