Genetically Modified Rat Is Promising Model For Alzheimer's : Shots - Health News Drug companies have developed several Alzheimer's drugs that seemed to work in mice but did not help people with the disease. So scientists inserted human genes into rats in hopes of getting a better model for testing the drugs.

Genetically Modified Rat Is Promising Model For Alzheimer's

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The field of Alzheimer's research is about to get a boost from a very special rat. This week in the Journal of Neuroscience, there's a report about the first rodent to develop the full range of brain problems that affect people with Alzheimer's. Scientists hope the rat will lead to a better understanding of how the disease damages the brain and which drugs might halt its progress. NPR's Jon Hamilton explains.

JON HAMILTON, BYLINE: For about two decades now, researchers have been studying Alzheimer's disease using mice - not just any mice. These rodents carry the same human gene mutations that cause people to get the disease in their 40s and 50s. And Rod Corriveau of the National Institute of Neurological Disorders and Stroke says, in one important way, the brains of these mice do resemble those of Alzheimer's patients.

DR. ROD CORRIVEAU: The mice developed what's called plaques, amyloid plaques that can contain the protein fragment that's thought to cause Alzheimer's disease.

HAMILTON: But that's where the similarity ends. In people with Alzheimer's, after plaques appear, huge numbers of brain cells die. Corriveau says that's never happened in mice despite lots of genetic tinkering.

CORRIVEAU: And while we learn many things and came up with different varieties of Alzheimer's models, no matter what combinations they tried, there's still been this huge gap. There just haven't been a significant number of neurons dying.

HAMILTON: So Corriveau says researchers began to consider a different rodent model: the rat.

CORRIVEAU: The rats are 4 to 5 million years closer evolutionarily to humans, so let's try rats and maybe we'll get that feature of neuronal cell death.

HAMILTON: Researchers did try. They put various combinations of human Alzheimer's genes in rats. But it didn't work. Then a group of scientists began studying one particular family line of rats. Terrence Town, at the University of Southern California, says when these rats got older, they got some of the same health problems people do.

DR. TERRENCE TOWN: That's actually why we chose this line because we thought that they would be a sort of on the cusp of normal aging. And then if we added into that mix these mutant human genes that cause Alzheimer's, we might have a much better and much more full model of the human syndrome.

HAMILTON: Town says once they inserted the mutant genes, the rats began to develop plaques in their brains, just like the mice had. But he says, unlike the mice, the rats also developed so-called tangles in their brain cells, another hallmark of Alzheimer's.

TOWN: The big shocker came when we started counting numbers of neurons in their brains. And it turns out that they lose up to about 30 or 35 percent of the neurons in brain regions that are classically associated with human Alzheimer's disease.

HAMILTON: Something that had never happened in mice. And there was one more thing. Town says as the rats lost brain cells, they also began to lose their ability to do things like navigate a maze.

TOWN: They perform much more poorly on a variety of these tests of learning and memory. And in addition, as the animals age, they perform even worse, much as you would see in a human being that would have these mutations.

HAMILTON: Rod Corriveau, from the NIH, says the new rat model should give researchers a better way to study how amyloid plaques and tangles kill off brain cells. And, he says, it should allow something that's of more practical use to people with Alzheimer's.

CORRIVEAU: What it allows is the best possible opportunity to discover drugs that will work in humans. The closer the model is to the human condition in representing the disease, the more likely the drug will behave and cure the way it would in humans.

HAMILTON: Terrence Town says he's already begun testing drugs on the new rats. And he says lots of other scientists have asked to try these rats in their labs. Jon Hamilton, NPR News.

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