Transgenic C. elegans as a model in Alzheimer's research

Curr Alzheimer Res. 2005 Jan;2(1):37-45. doi: 10.2174/1567205052772768.


Alzheimer's disease (AD) has been associated with aggregation of beta-amyloid peptide (Abeta) and cell death in the brain. Using various models, such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the mouse Mus musculus, investigators have attempted to imitate the pathology process of AD for better understanding of the cellular mechanisms and for possible therapeutic intervention. Among many in vitro and in vivo models of AD, transgenic C. elegans expressing human Abeta has shown its own advantages. The transgenic C. elegans model have been used in studying AD due to its short life span, facility to maintain, ability to develop muscle-associated deposits reactive to amyloid-specific dyes and the concomitant progressive paralysis phenotype. Moreover, the transgenic C. elegans exhibits increased levels of reactive oxygen species (ROS) and protein carbonyls, similar to those observed in AD patients, supporting the current theory on Abeta-induced oxidative stress and subsequent neurodegeneration in AD. DNA microarray assays of the worm demonstrated several stress-related genes being upregulated, particularly two genes homologous to human alphaB-crystallin and tumor necrosis factor-related protein, which were also upregulated in postmortem AD brain. Studies in our laboratory along with others suggest that the transgenic C. elegans model is a suitable in vivo model to relate Abeta-expression with its toxicity, which may underlie AD pathology. It may also be used as a tool for pharmacological evaluation of novel therapeutic agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology*
  • Animals
  • Caenorhabditis elegans
  • Disease Models, Animal*
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis / methods
  • Oxidative Stress / physiology
  • Phenotype
  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor Decoy Receptors
  • Up-Regulation


  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor Decoy Receptors
  • recombinant human tumor necrosis factor-binding protein-1