Brain Cytochrome Oxidase Activity and How it Relates to the Pathophysiology of Memory and Alzheimer’s Disease

Abstract

Recent studies indicate that mitochondrial electron transport dysfunction is involved in various neurodegenerative diseases, including Alzheimer’s disease. Although much attention has been devoted to Alzheimer’s disease, relatively little has been devoted to the role of oxidative energy metabolism in this disease. Whether genetic or environmental, the pathogenesis of Alzheimer’s disease involves a cascade of multiple intracellular events, eventually resulting in failure of oxidative energy metabolism. It is proposed that impairment of cytochrome oxidase activity in energy metabolism initiates the degenerative process by the formation of reactive oxygen species and free radicals. Brain energy failure was produced in an animal pharmacological model based on cytochrome oxidase enzymatic inhibition with sodium azide. Quantitative cytochemical methods for assessing cytochrome oxidase activity in individual neurons are discussed in relationship to the selective vulnerability of larger projection neurons in Alzheimer’s brains. Cytochrome oxidase activity is discussed in relationship to neuronal oxidative metabolism, memory and Alzheimer’s disease.