Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles.
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.
Wittmann
C W
CW
Department of Pathology, Division of Neuropathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, MA 02115, USA.
Wszolek
M F
MF
Shulman
J M
JM
Salvaterra
P M
PM
Lewis
J
J
Hutton
M
M
Feany
M B
MB
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D009154:Mutation; D009410:Nerve Degeneration; D009411:Nerve Endings / Q000378:metabolism / Q000648:ultrastructure; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D019581:Neuropil / Q000648:ultrastructure; D010766:Phosphorylation; D014617:Vacuoles / Q000648:ultrastructure; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D016875:tau Proteins; D000109:Acetylcholine