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Journal of Aging Research
Volume 2012 (2012), Article ID 324968, 9 pages
http://dx.doi.org/10.1155/2012/324968
Review Article

New Insights in the Amyloid-Beta Interaction with Mitochondria

Department of Pathology and Neuropathology, Hospital of Meixoeiro, University Hospital of Vigo, Meixoeiro s/n, 36215 Vigo, Spain

Received 28 November 2011; Accepted 11 January 2012

Academic Editor: Jan Vijg

Copyright © 2012 Carlos Spuch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD). Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP) has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both proteins are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron transport chain, increase reactive oxygen species production, cause mitochondrial damage, and prevent neurons from functioning normally. In this paper, we will outline current knowledge of the intracellular localization of amyloid-beta. Moreover, we summarize evidence from AD postmortem brain as well as animal AD models showing that amyloid-beta triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. Thus, this paper supports the Alzheimer cascade mitochondrial hypothesis such as the most important early events in this disease, and probably one of the future strategies on the therapy of this neurodegenerative disease.