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Aβ in Mitochondria—One Piece in the Alzheimer’s Disease Puzzle

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Studies on Alzheimer's Disease

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Abstract

Although great advances have been made in our understanding of the neurodegenerative process in Alzheimer’s disease (AD), the complete picture has not emerged and there are still pieces missing. One attractive hypothesis is that mitochondrial failure is a cause of synapse loss and cognitive impairment in AD. ATP generation by mitochondria is crucial for proper synaptic function and therefore neurons are highly sensitive to mitochondrial damage potentially leading to synapse loss and cognitive dysfunction. Several evidences indicate that mitochondria are indeed damaged and dysfunctional in the AD brain; these include mitochondrial accumulation of amyloid β-peptide (Aβ), impaired brain glucose metabolism, impaired mitochondrial fusion/fission, and increased generation of reactive oxygen species (ROS). In this chapter we will focus on the role of Aβ in mitochondria and discuss mitochondrial uptake mechanisms and interactions with mitochondrial proteins. Several evidences point towards a central role of Aβ initiating mitochondrial damage and generation of ROS in turn leading to synaptic and neuronal degeneration. Therefore, it would be of high importance to develop drugs that maintain mitochondrial integrity and prevent mitochondrial failure otherwise leading neuronal dysfunction.

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Authors and Affiliations

  1. Department of Neurobiology, Care Sciences and Society, KI-Alzheimer’s Disease Center (KI-ADRC), Karolinska Institutet, Novum 5th floor, Stockholm, SE-141 86, Sweden

    Maria Ankarcrona Ph.D.

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  1. Maria Ankarcrona Ph.D.
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Correspondence to Maria Ankarcrona Ph.D. .

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Editors and Affiliations

  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

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Ankarcrona, M. (2013). Aβ in Mitochondria—One Piece in the Alzheimer’s Disease Puzzle. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_5

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