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PubMed · 17168650

Mitochondrial dysfunction and Alzheimer's disease.

Xi Chen·David Stern·Shi Du Yan
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Abstract

Mitochondrial dysfunction has been implicated in causing metabolic abnormalities in Alzheimer's disease (AD). The searches for mitochondrial DNA variants associated with AD susceptibility have generated conflicting results. The age-related accumulation of somatic mitochondrial DNA deletion has been suggested to play a pathogenic role in the development of AD. Recent studies have demonstrated that amyloid-beta peptide (Abeta) progressively accumulates in mitochndrial matrix, as demonstrated in both transgenic mice over-expressing mutant amyloid precursor protein (APP) and autopsy brain from AD patients. Abeta-mediated mitochondrial stress was evidenced by impaired oxygen consumption and decreased respiratory chain complexes III and IV activities in brains from AD patients and AD-type transgenic mouse model. Furthermore, our studies indicated that interaction of intramitochondrial Abeta with a mitochondrial enzyme, amyloid binding alcohol dehydrogenase (ABAD), inhibits its enzyme activity, enhances generation of reactive oxygen species (ROS), impairs energy metabolism, and exaggerates Abeta-induced spatial learning/memory deficits and neuropathological changes in transgenic AD-type mouse model. Interception of ABAD-Abeta interaction may be a potential therapeutic strategy for Alzheimer's disease.

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Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsDNA, MitochondrialHumansMiceMitochondrial DiseasesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tReview

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Xi Chen, David Stern, Shi Du Yan. 2006. Mitochondrial dysfunction and Alzheimer's disease.. https://doi.org/10.2174/156720506779025215

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