Current Alzheimer Research

Prof. Debomoy K. Lahiri  
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202
USA

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Mitochondrial Dysfunction and Alzheimers Disease

Author(s): Xi Chen, David Stern and Shi Du Yan

Affiliation: Department of Pathology, Surgery, and Taub Institute for Research on Alzheimer's Disease and the Ageing Brain, College of Physician&Surgeons of Columbia University, 650 West 168th Street, New York, NY 10032, USA.

Keywords: cytochrome c oxidase (COX), reactive oxygen species (ROS), AD-specific mtDNA variants, amyloid precursor protein, ABAD interaction

Abstract:

Mitochondrial dysfunction has been implicated in causing metabolic abnormalities in Alzheimers 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 (Aβ) progressively accumulates in mitochndrial matrix, as demonstrated in both transgenic mice over-expressing mutant amyloid precursor protein (APP) and autopsy brain from AD patients. Aβ-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 Aβ 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 Aβ-induced spatial learning/memory deficits and neuropathological changes in transgenic AD-type mouse model. Interception of ABAD-Aβ interaction may be a potential therapeutic strategy for Alzheimers disease.

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Article Details

VOLUME: 3
ISSUE: 5
Page: [515 - 520]
Pages: 6
DOI: 10.2174/156720506779025215