Mouse study: Signal overload in Alzheimer brains

In studies with mice that develop the equivalent of Alzheimer’s disease that runs in families, Johns Hopkins researchers have shown that brain cells’ signals confuse the movement of implanted neuronal stem cells.

The observation reinforces the idea that disease can create “microenvironments” that affect the behavior of cells. These local environments might help recruit stem cell-based therapies in other conditions, say the researchers. The findings are to be presented Oct. 25 at the annual meeting of the Society for Neuroscience by first author Zhiping Liu, Ph.D., a research associate in pathology.

“In normal adult mice, stem cells taken from the olfactory bulb returned to the olfactory bulb — they returned to where they belong — even though they had come from a different mouse,” says Lee Martin, Ph.D., associate professor of pathology and neuroscience at Hopkins. “In mice with Alzheimer’s disease, the stem cells went all over the place within the brain, responding to a multitude of signals whose identities we don’t even know.”

Remarkably, Martin says, the stem cells were attracted to the abnormal protein bundles called amyloid plaques that cause Alzheimer’s, possibly opening the door to delivering some sort of plaque-buster. Because Alzheimer’s is characterized by a relatively global loss of brain cells, rather than loss of a particular group of cells, stem cells themselves aren’t as likely to be beneficial as in diseases where the loss is focused, such as amyotrophic lateral sclerosis and Parkinson’s disease.

The olfactory bulb, the center of smell detection, houses numerous primitive stem cells that normally feed the constant, life-long regeneration of odor-detecting nerves. Because they are found in a fairly accessible region of the brain and could conceivably be removed from a person’s olfactory bulb without causing permanent damage, adult olfactory bulb stem cells are a potential non-embryonic source for cells that could prove useful in replacing nerve cells lost due to injury or diseases like ALS and Parkinson’s.

The mice in the study were actually serving as controls for a study of stem cells in mice that develop amyotrophic lateral sclerosis, to see how the stem cells behaved in other models of neurodegenerative diseases.