ENERGY-METABOLISM, OXIDATIVE STRESS AND NEURONAL DEGENERATION IN ALZHEIMERS-DISEASE

Both altered energy metabolism and oxidative stress have been proposed to contribute to tissue damage in neurogenerative diseases. Animal mo dels and cell culture studies provide evidence for a role of these pro cesses in several forms of neuronal death. Reductions in the activitie s 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 glucose in vivo indicate that a reduced functional capacity of mitochondria is probabl y not a general feature in the brain in Alzheimer's disease. These stu dies 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 incr ease in oxidative damage in those areas of brain which are most severe ly affected in this disease, probably resulting from an increase in pr oduction of reactive oxygen species. Whether this is a contributor to neurodegeneration or a consequence of it remains unresolved. (C) 1996 Academic Press Limited