RT Journal Article SR Electronic T1 Mitochondrial Abnormalities in Alzheimer's Disease JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3017 OP 3023 DO 10.1523/JNEUROSCI.21-09-03017.2001 VO 21 IS 9 A1 Hirai, Keisuke A1 Aliev, Gjumrakch A1 Nunomura, Akihiko A1 Fujioka, Hisashi A1 Russell, Robert L. A1 Atwood, Craig S. A1 Johnson, Anne B. A1 Kress, Yvonne A1 Vinters, Harry V. A1 Tabaton, Massimo A1 Shimohama, Shun A1 Cash, Adam D. A1 Siedlak, Sandra L. A1 Harris, Peggy L. R. A1 Jones, Paul K. A1 Petersen, Robert B. A1 Perry, George A1 Smith, Mark A. YR 2001 UL http://www.jneurosci.org/content/21/9/3017.abstract AB The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situhybridization to mitochondrial DNA (mtDNA), immunocytochemistry 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 by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant 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 analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease.