title: Increased autophagic degradation of mitochondria in Alzheimer disease.
abstract: Extensive literature exists supporting a role for mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer disease. Mitochondria are a major source of intracellular reactive oxygen species and are themselves particularly vulnerable to oxidative stress. It has been recently shown that the immunoreactivity of lipoic acid and cytochrome oxidase-1, two mitochondrial markers, is increased in the cytoplasm of pyramidal neurons in Alzheimer disease cases compared with controls. Furthermore, lipoic acid was found to be strongly associated with granular structures and, by ultrastructure analysis, shown to be localized in mitochondria, cytosol and, importantly, in organelles identified as autophagic vacuoles. Lipoic acid was also found associated with the electron dense core of lipofuscin in the brains of Alzheimer disease cases but not in controls, whereas cytochrome oxidase-1 immunoreactivity was limited to mitochondria and cytosol in both Alzheimer and control cases. These data suggest that mitochondria are key targets of increased autophagic degradation in Alzheimer disease. The study of autophagy in Alzheimer disease could clarify the mechanisms underlying this neurodegenerative disorder and, eventually, help in the development of new therapeutic strategies.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Siedlak
authors.forename: Xinglong
authors.initials: X
authors.lastname: Wang
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Massimo
authors.initials: M
authors.lastname: Tabaton
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Luke I
authors.initials: LI
authors.lastname: Szweda
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress