Inhibition of Cytochrome Oxidase Impairs Learning and Hippocampal Plasticity: A Novel Animal Model of Alzheimer\u27s Disease

Patients suffering from Alzheimer’s disease (AD), as well as other dementing disorders, show global decreases in markers of cerebral metabolism such as blood flow, oxygen uptake and glucose utilization (Phelps, Mazziotta, and Huang, 1982). The question arises, however, as to whether these changes are of etiological significance. Blass, Sheu and Cedarbaum (1988) have distinguished between primary, secondary and tertiary disorders of energy metabolism. A primary disorder is a defect of the cellular machinery of energy metabolism. These defects are inborn errors and primarily affect the CNS. The CNS is more sensitive to a decline in energy metabolism than other organs are, and is therefore a major target of damage when this function is impaired. A secondary disorder of energy metabolism is not metabolic in origin, but rather a consequence of a triggering pathology which damages mitochondrial function. Sequelae from the subsequent dysfunction of energy metabolism, then, produce cellular pathology and contribute to the overall disease process. A tertiary disorder of energy metabolism is one in which the abnormal markers of energy metabolism are purely a consequence of neuronal degeneration. In the latter class, the decline in energy metabolism occurs late in the disease and is trivial as a pathophysiological process in the disease. The classification of AD within this schema is unknown