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Cited by 395Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer’s disease: Implications to mitochondria-targeted antioxidant therapeutics

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Reddy, P. Hemachandra, Tripathi, Raghav, Troung, Quang, Tirumala, Karuna, Reddy, Tejaswini P., Anekonda, Vishwanath, Shirendeb, Ulziibat P., Calkins, Marcus J. +3 more·2012·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI 10.1016/j.bbadis.2011.10.011PMC PMC3272314
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Abstract

Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer's disease (AD) progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. Recent research on amyloid beta (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

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Crossref · 10.1016/j.bbadis.2011.10.011

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  • Oxidative stress, mitochondrial dysfunction, and glucose hypometabolism have been well documented in MCI and AD brain.

    “However, oxidative stress, mitochondrial dysfunction, and glucose hypometabolism have been well documented in MCI and AD brain [8,53,74,75,76].”

    From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [53]

    Sections 3.1 and 3.5 report reduced brain glucose metabolism, oxidative stress, and mitochondrial dysfunction in AD. The passages do not establish these findings in MCI brain, so the claim’s extension to MCI is unsupported by this source. (LLM, conf=0.88)

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  • Redox proteomics has led to identification of oxidized proteins, indexed by carbonylation, nitration, and modification with HNE, in in vitro and in vivo models of AD and in MCI and AD brain.

    “As mentioned above, the use of redox proteomics has led to the identification of oxidized proteins, as indexed by carbonylation, nitration, and modification with HNE, in both in vitro and in vivo models of AD in addition to MCI and AD brain.”

    From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [53]

    Section 3.5 (page unavailable) reports oxidative protein damage in postmortem AD brain and oxidative stress in AD mouse and neuronal models. It does not say that redox proteomics identified oxidized proteins using carbonylation, nitration, or HNE modification, or report such findings in MCI brain. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Compelling evidence links neurodegeneration to altered brain metabolism and mitochondrial dysfunction, both of which are early hallmarks of Alzheimer's disease.

    “Compelling evidence links neurodegeneration to altered brain metabolism and mitochondrial dysfunction, both of which are early hallmarks of AD [21–28].”

    From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [27]

    Section 3.1 reports reduced brain glucose metabolism in AD, and sections 3 and 4.0 link mitochondrial dysfunction to AD pathology, including early deficits in a mouse model. The paper does not establish that altered brain metabolism itself is an early hallmark of AD; its glucose-metabolism passage does not address timing. No page numbers are available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Many of the oxidized proteins identified are mitochondrial proteins involved in metabolism, protein synthesis and folding, ROS scavenging, transport, and apoptosis.

    “Consistent with the hypothesis that both oxidative stress and mitochondrial dysfunction are early events in the progression of AD [12,35,53], many of the oxidized proteins identified are mitochondrial proteins involved in metabolism, protein synthesis and folding, ROS scavenging, transport, and apoptosis (Table 1).”

    From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [53]

  • The presence of Aβ oligomers in mitochondrial membranes is consistent with Aβ-induced mitochondrial dysfunction occurring early in the disease progression timeline.

    “The presence of Aβ oligomers in mitochondrial membranes is consistent with Aβ-induced mitochondrial dysfunction occurring early in the disease progression timeline [34,53].”

    From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [53]

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Authors
Reddy, P. H., Tripathi, R., Troung, Q., Tirumala, K., Reddy, T. P., Anekonda, V., Shirendeb, U. P., Calkins, M. J., Reddy, A. P., Mao, P., & Manczak, M.
Affiliations
Oregon National Primate Research Center (US)
Corresponding author
Reddy, P. Hemachandra
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2012-05
Volume
1822
Issue
5
Pages
639-649
ISSN
0925-4439 (ISSN-L)
DOI
10.1016/j.bbadis.2011.10.011
PMC
PMC3272314
OpenAlex
W1996981671
Cited by
394
References
104
Citations by year
2026: 29 · 2025: 17 · 2024: 22 · 2023: 27 · 2022: 30 · 2021: 38 · 2020: 29 · 2019: 30 · 2018: 26 · 2017: 36 · 2016: 31 · 2015: 19 · 2014: 31 · 2013: 18 · 2012: 10
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH
  • Alzheimer Association
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 dynamics, synaptic degeneration, amyloid-beta, mitochondrial oxidative damage, mitochondrial biogenesis, mitochondria-targeted antioxidants, antioxidant therapeutics, synaptic mitochondria
MeSH terms
Alzheimer Disease, Animals, Antioxidants, Humans, Mice, Transgenic, Mitochondria, Synapses, Amyloid beta-Protein Precursor, Mice

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