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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 925050, 12 pages
Review Article

Amyloid-Beta Interaction with Mitochondria

Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Wilhelm Klein-Straße 27, 4012 Basel, Switzerland

Received 22 November 2010; Accepted 22 December 2010

Academic Editor: Katsuhiko Yanagisawa

Copyright © 2011 Lucia Pagani and Anne Eckert. 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.


Mitochondrial dysfunction is a hallmark of amyloid-beta(Aβ)-induced neuronal toxicity in Alzheimer's disease (AD). The recent emphasis on the intracellular biology of Aβ and its precursor protein (AβPP) has led researchers to consider the possibility that mitochondria-associated and/or intramitochondrial Aβ may directly cause neurotoxicity. In this paper, we will outline current knowledge of the intracellular localization of both Aβ and AβPP addressing the question of how Aβ can access mitochondria. Moreover, we summarize evidence from AD postmortem brain as well as cellular and animal AD models showing that Aβ triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species (ROS) production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. In particular, we focus on Aβ interaction with different mitochondrial targets including the outer mitochondrial membrane, intermembrane space, inner mitochondrial membrane, and the matrix. Thus, this paper establishes a modified model of the Alzheimer cascade mitochondrial hypothesis.