Dementia

08 September 2006

New enzyme fights Alzheimer's

Researchers think they may have found a way to target neurofibrillary tangles, the jumbled bits of protein inside brain cells that might contribute to Alzheimer's disease.

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Researchers think they may have found a way to target neurofibrillary tangles, the jumbled bits of protein inside brain cells that might contribute to Alzheimer's disease.

In tests with mice and fruit flies, an enzyme appeared to both eliminate the tangles and reduce the brain's decline. "The research is in an early stage. However, the approach is both unique and promising," said study co-author Dr Daniel Geschwind, professor of neurology, psychiatry and human genetics at the University of California, Los Angeles.

"We've shown in animals that this is working," Geschwind said. "I think it's very viable, but one needs to prove that."

Much of Alzheimer's research has focused on so-called amyloid plaques, a buildup of proteins inside the brain between cells that appears to contribute to dementia. But Geschwind and his colleagues looked at tangles, another part of the puzzle. These tangles of protein, called tau, are associated with cognitive decline in Alzheimer's and similar "tauopathy" diseases.

Neurofibrillary tangles are "a kind of compressed bunch of filaments that are just like a tangled bit of twine inside the [brain] cell," Geschwind said.

Tangles in the brain
It's not clear if tangles hurt brain cells or are just a symptom of a dementia problem. "The point is that they're totally correlated with neurodegeneration in Alzheimer's disease, and in a number of other dementias," he said.

In some forms of dementia, tangles are "the whole story" because amyloid plaques aren't present, said Dr Sam Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

Geschwind and his colleagues suspected that an enzyme known as puromycin-sensitive aminopeptidase plays a role in degenerating brains. They tried to see if the enzyme would affect brain cells in mice that had been genetically engineered to suffer from neural degeneration that was similar to Alzheimer's in humans.

The scientists launched a similar effort in fruit flies. "While fruit flies may not seem like the brainiest of species, the researchers simulated Alzheimer's by causing degeneration in the cells of their eyes," Geschwind said.

Preventative enzyme
The researchers found that the enzyme appeared to prevent both the decline of brain cells and snip apart tangles. Research on brain cells taken from humans suggested that the scientists are on the right track. The findings are published in the September 7 issue of the journal Neuron.

According to Geschwind, the findings may have implications not only for Alzheimer's disease but other similar disorders, including frontotemporal dementia (also known as Pick's disease), progressive supranuclear palsy (which killed actor Dudley Moore) and corticobasal degeneration.

"However, it will likely take years for a drug for humans to be developed," Geschwind said. For now, there is no cure for Alzheimer's disease, although some drugs treat its symptoms. "Still, the new findings are promising," Gandy said, "especially considering that research into tangles has lagged behind research into ways to combat amyloid plaques." -(HealthDayNews, September 2006)

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