LOS ANGELES ---- 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
But there's a lot that scientists don't yet understand. And, as
we know, effective treatments for Alzheimer's are thin on the
A study recently 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 sprang 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
Then the researchers did the 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 Aa42.
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 also have 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 something else.
The authors of this 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.