Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles

Science. 2001 Jul 27;293(5530):711-4. doi: 10.1126/science.1062382. Epub 2001 Jun 14.


The microtubule-binding protein tau has been implicated in the pathogenesis of Alzheimer's disease and related disorders. However, the mechanisms underlying tau-mediated neurotoxicity remain unclear. We created a genetic model of tau-related neurodegenerative disease by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila melanogaster. Transgenic flies showed key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary tangle formation that is seen in human disease and some rodent tauopathy models. This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Aging
  • Animals
  • Animals, Genetically Modified
  • Brain / pathology
  • Brain / ultrastructure
  • Disease Models, Animal*
  • Drosophila melanogaster* / genetics
  • Humans
  • Mutation
  • Nerve Degeneration
  • Nerve Endings / metabolism
  • Nerve Endings / ultrastructure
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Neurofibrillary Tangles / ultrastructure
  • Neurons / metabolism
  • Neurons / ultrastructure*
  • Neuropil / ultrastructure
  • Phosphorylation
  • Vacuoles / ultrastructure
  • tau Proteins / chemistry
  • tau Proteins / genetics
  • tau Proteins / metabolism*


  • tau Proteins
  • Acetylcholine