Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles.

Authors: Wittmann CW; Wszolek MF; Shulman JM; Salvaterra PM; Lewis J; Hutton M; Feany MB

Abstract: 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.

Keywords: Acetylcholine/metabolism; Aging; Animals; Animals, Genetically Modified; Brain/pathology/ultrastructure; *Disease Models, Animal; *Drosophila melanogaster/genetics; Humans; Mutation; Nerve Degeneration; Nerve Endings/metabolism/ultrastructure; Neurodegenerative Diseases/metabolism/*pathology; Neurofibrillary Tangles/ultrastructure; Neurons/metabolism/*ultrastructure; Neuropil/ultrastructure; Phosphorylation; Vacuoles/ultrastructure; tau Proteins/chemistry/genetics/*metabolism
Journal: Science (New York, N.Y.)
Volume: 293
Issue: 5530
Pages: 711-4
Date: June 16, 2001
PMID: 11408621
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Citation:

Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, Hutton M, Feany MB (2001) Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science (New York, N.Y.) 293: 711-4.


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