Cited by 177Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Mitochondrial dysfunction - the beginning of the end in Alzheimer's disease? Separate and synergistic modes of tau and amyloid-β toxicity

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Eckert, Anne, Schmitt, Karen, Götz, Jürgen·2011·Alzheimer's Research & Therapy

Abstract

The pathology of Alzheimer's disease (AD) is characterized by amyloid plaques (aggregates of amyloid-β (Aβ)) and neurofibrillary tangles (aggregates of tau) and is accompanied by mitochondrial dysfunction, but the mechanisms underlying this dysfunction are poorly understood. In this review, we discuss the critical role of mitochondria and the close inter-relationship of this organelle with the two main pathological features in the pathogenic process underlying AD. Moreover, we summarize evidence from AD post-mortem brain as well as cellular and animal AD models showing that Aβ and tau protein trigger 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. A vicious cycle as well as several vicious circles within the cycle, each accelerating the other, can be drawn, emphasizing the synergistic deterioration of mitochondria by tau and Aβ.

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  • Aβ inhibits the activity of key mitochondrial enzymes such as electron transport chain enzyme complex IV, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase, reducing electron transfer efficiency, diminishing ATP synthesis, and stimulating ROS production.

    “Aβ inhibits the activity of key mitochondrial enzymes such as electron transport chain enzyme complex IV, pyruvate dehydrogenase (PDH), and α-ketoglutarate dehydrogenase (αKGDH), reducing the efficiency of electron transfer, diminishing ATP synthesis, and stimulating the production of ROS.286”

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Authors
Eckert, A., Schmitt, K., & Götz, J.
Affiliations
  • University of Basel (CH)
  • The University of Sydney (AU)
Corresponding author
Eckert, Anne
Venue
Alzheimer's Research & Therapy
Published
2011
Volume
3
Issue
2
Pages
15
ISSN
1758-9193 (ISSN-L)
OpenAlex
W1973417023
Cited by
177
References
73
Citations by year
2026: 14 · 2025: 14 · 2024: 7 · 2023: 8 · 2022: 12 · 2021: 16 · 2020: 13 · 2019: 10 · 2018: 13 · 2017: 4 · 2016: 16 · 2015: 12 · 2014: 3 · 2013: 14 · 2012: 14
FWCI
8.07
Type
journal article
Language
en
Open access
Locations
  • Alzheimer s Research & Therapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, mitochondrial dysfunction, amyloid-beta, tau protein, oxidative phosphorylation, reactive oxygen species, mitochondrial dynamics, neurofibrillary tangles, amyloid plaques, synergistic toxicity, vicious circle

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