title: Mitochondrial dysfunction and Alzheimer's disease.
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.
authors.affiliation: Department of Neurology and Veteran Administration Medical Center, School of Medicine, Saint Louis University, St. Louis, MO 63106, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Stern
authors.forename: Shi Du
authors.initials: SD
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D006801:Humans; D051379:Mice; D028361:Mitochondrial Diseases / Q000150:complications*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004272:DNA, Mitochondrial