Cited by 371Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid β-peptide (1–42) in a transgenic Caenorhabditis elegans model

Drake, J·2003·Neurobiology of Aging

Abstract

Alzheimer's disease is a progressive, neurodegenerative disorder characterized by senile plaques and neurofibrillary components. Abeta(1-42) is a principal component of senile plaques and is thought to be central to the pathogenesis of the disease. The Alzheimer's disease brain is under significant oxidative stress, and the Abeta(1-42) peptide is known to cause oxidative stress in vitro. One controversy in the amyloid hypothesis is whether or not Abeta plaques are required for toxicity. We have employed a temperature-inducible Abeta expression system in Caenorhabditis elegans to create a strain of worms, CL4176, in which Abeta(1-42) is expressed with a non-permissive temperature of 23 degrees C. The CL4176 strain allows examination of the temporal relationship between Abeta expression, oxidative stress, and Abeta fibril formation. CL4176 were under increased oxidative stress, evidenced by increased protein oxidation indexed by increased carbonyl levels, 24 and 32 h after temperature upshift as compared to the control strain, CL1175. The increased oxidative stress in CL4176 occurred in the absence of Abeta fibril formation, consistent with the notion that the toxic species in Abeta toxicity is pre-fibrillar Abeta and not the Abeta fibril. These results are discussed with reference to Alzheimer's disease.

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Crossref · 10.1016/s0197-4580(02)00225-7

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  • Oligomeric Aβ rather than fibril Aβ is regarded as the toxic species of this peptide.

    “oligomeric Aβ rather than fibril Aβ is regarded as the toxic species of this peptide [143,144,145,146].”

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Authors
Drake, J.
Affiliations
University of Kentucky (US)
Corresponding author
Drake, J
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2003-06
Volume
24
Issue
3
Pages
415-420
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2170111492
Cited by
371
References
50
Citations by year
2026: 8 · 2025: 8 · 2024: 14 · 2023: 10 · 2022: 21 · 2021: 21 · 2020: 18 · 2019: 10 · 2018: 11 · 2017: 12 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 15 · 2012: 14
FWCI
15.37
Type
journal article
Language
en
Open access
closed
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (P01AG010836, P01AG005119, AG 10836, AG12423, AG0 5119, R01AG012423)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid-beta, amyloid-beta 42, oxidative stress, protein oxidation, amyloid fibril formation, amyloid hypothesis, amyloid plaques, Caenorhabditis elegans, transgenic worms, temperature-inducible expression, carbonyl compounds
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Neurofibrils, Oxidation-Reduction, Peptide Fragments, Protein O-Methyltransferase, Gene Expression, Amyloid beta-Peptides, Caenorhabditis elegans, Oxidative Stress, Animals, Genetically Modified, Plaque, Amyloid

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