In Alzheimer's disease and related dementias, neurons die stuffed with cellular debris, consisting mainly of a protein called tau. Now a new fruit fly burdened with tau loses brain cells when it gets old. The model could help uncover new clues about how tau might torpedo neurons.
Tau normally stabilizes neuron microtubules, a kind of rail system that runs through neurons and helps transport molecules to nerve endings. In Alzheimer's and other diseases, tau proteins clump together into tangles. Some researchers speculate that neurons are killed by tangles that gum up their internal works, although others suggest that free-floating tau does the damage, perhaps by causing oxidative damage or urging cells to kill themselves.
To find out how tau damages neurons, neuropathologist Mel Feany of Harvard Medical School in Boston and her colleagues introduced into fruit flies either the normal human tau gene or a mutant version responsible for another type of tau-related dementia. The researchers then watched what happened to the nervous systems of the transgenic flies as they aged. Brain cells in day-old flies were fine, but neurons in doddering 30-day-old flies had disintegrating nuclei and other organelles. "We saw them falling apart," Feany says. Both tau proteins especially damaged neurons that communicate using the neurotransmitter acetylcholine--a group of cells that are also hit heavily in Alzheimer's disease. Surprisingly, however, the dying neurons didn't contain any tangles, the researchers report in work published online by [http://www.sciencexpress.org] Science on 14 June.
It's "very elegant, nicely done work," says Zaven Khachaturian, senior scientific adviser to the Alzheimer's Association. But some experts caution that the lack of tangles might mean that flies aren't a good model of human dementias. "The worry is that cells are dying by a different mechanism than neurons do when they make tangles in Alzheimer's disease," says neuroscientist John Hardy of the Mayo Clinic in Jacksonville, Florida.