Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease

• Published in: Journal of Alzheimer's disease 2006-07, Vol.9 (2), p.147-153
• Main Authors: Zhu, Xiongwei, Perry, George, Moreira, Paula I., Aliev, Gjumrakch, Cash, Adam D., Hirai, Keisuke, Smith, Mark A.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Animals; Biological Transport - physiology; Cell Cycle - physiology; Free Radicals - adverse effects; Humans; Mitochondria - metabolism; Mitochondria - physiology; Neurons - physiology; Oxidative Stress - physiology
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-2006-9207

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.