Affiliations: [a] Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA | [b] Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA | [c] Dean's Office, University of Cincinnati College of Medicine, Cincinnati OH 45267, USA | [x] Center for Neuroscience and Cell Biology, Institute of Physiology – Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal | [y] Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
Correspondence:
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Corresponding author: David M. Stern, M.D., Dean's Office, College of Medicine, 231 Albert Sabin Way, University of Cincinnati Medical Center, PO Box 670555, Cincinnati, OH 45267-0555, USA. Tel.: +1 513 558 7333; Fax: +1 513 558 3512; E-mail: [email protected].
Abstract: Mitochondrial and metabolic dysfunction have been linked to Alzheimer's disease for some time. Key questions regarding this association concern the nature and mechanisms of mitochondrial dysfunction, and whether such changes in metabolic properties are pathogenic or secondary, with respect to neuronal degeneration. In terms of mitochondria and Alzheimer's, altered function could reflect intrinsic properties of this organelle, potentially due to mutations in mitochondrial DNA, or extrinsic changes secondary to signal transduction mechanisms activated in the cytosol. This review presents data relevant to these questions, and considers the implication of recent findings demonstrating the presence of amyloid-β peptide in mitochondria, as well as intra-mitochondrial molecular targets with which it can interact. Regardless of the underlying mechanism(s), it is likely that mitochondrial dysfunction contributes to oxidant stress which is commonly observed in brains of patients with Alzheimer's and transgenic models of Alzheimer's-like pathology.
