title: Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease.
abstract: A number of mitochondrial and metabolic abnormalities were identified in the hippocampal neurons of Alzheimer disease compared to age-matched controls. Hippocampal neurons are the most vulnerable to disease-associated pathology (i.e., cell death and proteinaceous lesions) and contain numerous markers of oxidative stress. Interestingly we found that the levels of mitochondrial DNA and cytochrome oxidase-1 in these neurons are markedly increased compared with those of age-matched control brains, even though the number of mitochondria per neuron is decreased. We hypothesize that the increased levels of mitochondrial DNA and cytochrome oxidase-1 may reflect an attempt by oxidatively-challenged neurons to replicate mitochondria, albeit unsuccessfully, as a response to the energetic/oxidative stress. Indeed, in this context, numerous signs of mitosis are observed in pyramidal neurons. Mitotic signals that promote cell cycle re-entry might be expected to also signal the synthesis of new mitochondria. Alternatively, these abnormalities may indicate altered turnover of mitochondrial components as a result of reduced degradation of mitochondrial byproducts or altered mitochondrial transport that redistributes mitochondrial DNA and cytochrome oxidase-1 to the cell body.
authors.affiliation: Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
authors.forename: Adam D
authors.initials: AD
authors.lastname: Cash
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hirai
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D005609:Free Radicals / Q000009:adverse effects; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D005609:Free Radicals