Mitochondrial abnormalities in Alzheimer's disease

The finding that oxidative damage, including that to nucleic acids, in Alzh eimer's disease is primarily limited to the cytoplasm of susceptible neuron al populations suggests that mitochondrial abnormalities might be part of t he spectrum of chronic oxidative stress of Alzheimer's disease. In this stu dy, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytoc hemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked b y 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons show ing increased oxidative damage in Alzheimer's disease have a striking and s ignificant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric an alysis showed that mitochondria are significantly reduced in Alzheimer's di sease. The relationship shown here between the site and extent of mitochond rial abnormalities and oxidative damage suggests an intimate and early asso ciation between these features in Alzheimer's disease.