Mitochondrial Abnormalities in Alzheimer’strongsstrong Disease.pdfVIP

The Journal of Neuroscience, May 1, 2001, 21(9):3017–3023 Mitochondrial Abnormalities in Alzheimer’s Disease Keisuke Hirai,1,4 Gjumrakch Aliev,2 Akihiko Nunomura,1,5 Hisashi Fujioka,1 Robert L. Russell,1 Craig S. Atwood,1 Anne B. Johnson,6 Yvonne Kress,6 Harry V. Vinters,7 Massimo Tabaton,8 Shun Shimohama,9 Adam D. Cash,1 Sandra L. Siedlak,1 Peggy L. R. Harris,1 Paul K. Jones,3 Robert B. Petersen,1 George Perry,1 and Mark A. Smith1 1Institute of Pathology, 2Department of Neurology, and 3Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, 4Pharmaceutical Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Osaka, 532-8686 Japan, 5Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa, 078-8510 Japan, 6Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 7 10461, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90024, 8Department of Neuroscience, University of Genova, 16132 Genova, Italy, and 9Department of Neurology, Kyoto University, Kyoto, 606-8507 Japan The finding that oxidative damage, including that to nucleic disease have a striking and significant increase in mtDNA and acids, in Alzheimer’s disease is primarily limited to the cyto- cytochrome oxidase. Surprisingly, much of the mtDNA and plasm of susceptible neuronal populations suggests that mito- cytochrome oxidase is found in the neuronal cytoplasm and in chondrial abnormalities might be part of the spectrum of the case of mtDNA, the vacuoles associated with lipofuscin. chronic oxidative stress of Alzheimer’s disease. In this study, we Morphometric analysis showed that