STEM CELLS IN ALZHEIMER'S RESEARCH BASIC INFORMATION

Because the mouse models of Alzheimer’s don’t truly duplicate the disease, researchers have tried making the genetic changes that cause early-onset Alzheimer’s in a variety of cells grown in the lab. This technique has been helpful in letting scientists understand how these genes work normally and what happens when they carry the mutations that cause Alzheimer’s.

However, until recently, scientists weren’t able to make and study these genetic changes in human neurons because, before the advent of human embryonic stem cells and technologies for reprogramming other cells, making human neurons in the lab was, for all practical purposes, impossible.

Scientists can use human stem cells — either embryonic stem cells or induced pluripotent stem cells from tissues — or neuronal stem cells from fetal tissue to grow human neurons that have the genetic mutations that lead to Alzheimer’s. Then they can study what’s different about those neurons and perhaps come up with drugs that repair the damage or keep the damage from spreading.

Similarly, scientists can take other types of cells — say, from the skin — from people with sporadic Alzheimer’s, reprogram them to become pluripotent stem cells, and grow neurons from them. (Larry’s lab at the University of California–San Diego is using this technique.) Then they can compare the behavior of human neurons with the genetic architecture of hereditary Alzheimer’s, sporadic Alzheimer’s, and normal neurons to see where the similarities and differences lie.

This comparison may help researchers determine why some people are less susceptible to Alzheimer’s than others, as well as identify the triggers and mechanisms of the disease — which may, in turn, lead to new therapies for treating Alzheimer’s. (Scientists are using similar approaches to study other diseases, too, such as Lou Gehrig’s and Parkinson’s.)

Scientists also are trying to find ways to use the brain’s own stem cells to replace damaged cells in Alzheimer’s and other diseases. Of course, growing neurons isn’t the only thing you can do with stem cells.

You can also

✓ Use them in cell transplant experiments. Several labs are experimenting with transplanting healthy cells into animals to see whether they replace or rescue damaged or defective cells in mouse models of Alzheimer’s.

✓ Use them to deliver material to specific regions of the brain. In Alzheimer’s patients, their brains may have enough of certain material, such as growth factors, but the material doesn’t get to the regions of the brain that need it. Scientists are exploring ways of using stem cells and other methods to deliver these potentially important materials to the appropriate parts of the brain.

✓ Use them to develop potential drug therapies. Scientists can test drug therapies on cells with hereditary or sporadic Alzheimer’s to see whether the therapies make the cells behave more normally.

Unfortunately, the idea of manipulating the brain’s own stem cells to solve problems outside their normal purview is easy to draw on a blackboard, but not so easy to put into practice. But it’s an exciting possibility with implications for all kinds of neurodegenerative diseases, so the scientific community is eagerly pursuing it.

For decades, researchers thought brains in humans and other mammals were devoid of stem cells. But the human brain (and animal brains, for that matter) does contain two small populations of stem cells. One cache supports the olfactory system (the tissues and organs involved in sensing smell), and the other is in a
region of the brain that’s involved in processing information and forming new memories.

Many researchers are trying to figure out whether these indigenous brain stem cells can be induced to provide rescue activity to regions that are damaged in Alzheimer’s and other neurodegenerative diseases. For example, perhaps these stem cells could be programmed to spawn new neurons to replace damaged or dead ones.