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

Jennifer Drake, Christopher D. Link, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

314 Scopus citations


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

Original languageEnglish
Pages (from-to)415-420
Number of pages6
JournalNeurobiology of Aging
Issue number3
StatePublished - 2003

Bibliographical note

Funding Information:
We would like to thank A. Taft for preparation of nematode samples, and A. Fire for providing the smg-1 -dependent vector used in the construction of the CL1175 and CL4176 strains. This work was supported by NIH grants to C.D.L. and D.A.B. [AG-12423] and D.A.B. [AG-05119; AG-10836].


  • Alzheimer's disease
  • Amyloid beta-peptide
  • Caenorhabditis elegans
  • Oxidative stress
  • Protein oxidation
  • Senile plaque

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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