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Published Online June 14, 2001
Science DOI: 10.1126/science.1062382

Reports

Submitted on May 9, 2001
Accepted on June 1, 2001

Tauopathy in Drosophila: Neurodegeneration Without Neurofibrillary Tangles

Curtis W. Wittmann 1, Matthew F. Wszolek 1, Joshua M. Shulman 1, Paul M. Salvaterra 2, Jada Lewis 3, Mike Hutton 3, Mel B. Feany 1*

1 Department of Pathology, Division of Neuropathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, MA 02115, USA.
2 Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.
3 Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.

* To whom correspondence should be addressed. E-mail: mel_feany{at}hms.harvard.edu.

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 have created a genetic model of tau-related neurodegenerative disease by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila. 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. Notably, however, neurodegeneration occurred without the neurofibrillary tangle formation that is seen in human disease and rodent tauopathy models. This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.


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