Molecular mechanisms of impaired mitochondrial gene expression in Alzheimer's disease

In vivo positron emission tomography imaging suggests that brain energy metabolism is reduced in patients with Alzheimer's disease. Tn vitro studies using postmortem brains from Alzheimer's disease patients show corresponding decreases in expression of mitochondrial genes encoding for enzymes of oxidative energy metabolism. Neurodegeneration and age-dependent deletions and mutations in mitochondrial DNA are among factors that have been proposed to be responsible for this reduction. Recent findings, however, suggest that reduced energy metabolism in Alzheimer's disease is coupled to reduced neuronal activity. It is proposed that in Alzheimer's disease, reduced synaptic input and downregulation of oxidative energy metabolism render neurons more vulnerable to sudden energy metabolic insults such as excitotoxicity and thereby hasten neurodegeneration.