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Creating nerve cells from skin cells offers Alzheimer's insights

August 04, 2011|By Rosie Mestel, Los Angeles Times / For the Booster Shots blog
  • Alzheimer's disease is poorly understood
Alzheimer's disease is poorly understood (Michael Morgenstern / For…)

What goes wrong in Alzheimer’s disease? Scientists know some things — that abnormal plaques derived from fragments of a protein called APP build up in the Alzheimer’s brain, for example, and that tangles of another protein, tau, build up too.

But there’s a lot that scientists don’t yet understand. And, as we know, effective treatments for Alzheimer’s are thin on the ground.

A study just published in the journal Cell may offer a better way to study what goes wrong in Alzheimer’s, its authors say, and also potentially provide a source of replacement tissues down the road, as well as a way to test drugs in the lab.

The researchers started with cultures of human skin cells growing in a dish — and turned them into nerve cells. They did this by infecting the cells with a few key genes, carried into the cells by a virus, and bathing the cells in the right cocktail of growth factors. The cells that resulted behaved like neurons in multiple ways. The correct genes sprung into action and the cells responded to neurotransmitters by letting ions like sodium and potassium in or out of cells the way neurons do. Other researchers had achieved the same thing with mouse nerve cells; the treatment required in this case was slightly different.

And when they were introduced into the brains of developing mice, the cells seemed to connect up properly with other brain cells.

Then the researchers did the exact same thing with skin cells obtained from people with an inherited form of Alzheimer’s. Again, the cells behaved like neurons — but they were clearly abnormal in the way that the protein APP was shuttled around the cell and cut up by certain enzymes. For example, in the Alzheimer’s cells there were greater amounts of a fragment from APP called Aβ42.

What the scientists found is already providing insights, they say, and they hope to expand their studies to the more numerous cases of so-called sporadic Alzheimer’s disease, where there isn’t a clear, strong genetic basis.

Researchers have high hopes that stem cells may one day provide replacement tissues — and thus maybe cures — for a range of diseases including Alzheimer’s as well as diabetes, Parkinson’s, spinal cord damage and more. (Bone marrow stem cells, of course, have long been used to treat cancers.)

But even more valuable to scientists in the short term is being able to use stem cells derived from people with diseases so they can study the cells in dishes and figure out what’s not working right, and use those cells to test drugs.

Embryonic stem cells have been considered the most promising in these pursuits because they are the most plastic — they can be turned into any tissue in the body. But political and regulatory issues don’t make them the easiest to work with.

In recent years, researchers have also figured out how to turn skin cells into cells that act pretty much like embryonic stem cells. But these man-made embryo cells, known as iPS cells, have their drawbacks. They’re hard to make and not super stable: You can turn them into a tissue and they may not stay that way, so some scientists are concerned about a possible cancer risk. Then, once you’ve got the cells, it takes a while to create the particular type of body cell that you want — be it a pancreas cell or a brain cell or whatever.

The authors of this new paper, headed by Columbia University researcher Asa Abeliovich, say their technique may have an edge on iPS cells because they made the nerve cells straight from skin cells with high efficiency, and relatively quickly too.

For more on the causes of Alzheimer’s disease and resources, here’s information from the National Institute of Neurological Disorders and Stroke.

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