Mitochondrial dysfunction - the beginning of the end in Alzheimer's disease? Separate and synergistic modes of tau and amyloid-β toxicity
Open accessAbstract
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”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [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)
- PMC
- PMC3226305
- 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
- gold
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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