Alzheimer’s May Impact Astrocytes

A group of researchers at Massachusetts General Hospital’s Institute for Neurodegenerative Disease (MIND) have discovered that the plaques associated with Alzheimer’s disease may affect a type of nervous system cell called an astrocyte, providing new insight into the far-reaching effects of the disease as well as possible therapeutic targets.

Astrocytes are star-shaped cells that make up almost half the volume of the brain, and were traditionally thought to be support cells. It is now known that they can transmit signals through transient increases in calcium levels.

“Astrocytes are often thought to play second fiddle to neurons but they play an ever increasing role in maintenance of the brain,” said Brian J. Bacskai, an associate professor of neurology at Harvard Medical School and one of the authors of the study.

The researchers used a mouse model for Alzheimer’s disease in the study to develop some of the pathology found in humans, including senile plaques.

They selectively labeled astrocytes with a marker that was bright when the cell was active and dimmer when it was inactive, said Kishore V.G.S. Kuchibhotla, a graduate student at Harvard and one of the authors.

Using state of the art optical microscopy that allowed them to image the mouse’s brain while the animal was still alive, the researchers found that the senile plaques modulated the activity of the astrocytes.

They discovered that the astrocytes in the mouse model for Alzheimer’s fired spontaneously more often than in a normal mouse and had increased levels of resting calcium.

“The astrocytes are connected over time and space and can send waves of calcium signals from one spot to the other,” said Bacskai, who added that these results were independent of neuronal activity.

Kuchibhotla said the researchers think that the plaque deposition may be seen as a traumatic event that is causing these intercellular calcium waves, providing a new line for Alzheimer’s therapy.

“Modulating the activity of astrocytes might be an interesting therapeutic target slightly different than the neurocentric view,” said Kuchibhotla.

Since this research can be applicable to other diseases—including Parkinson’s, Huntington’s, and Lou Gehrig’s disease—Bacskai and researchers at MIND are in the process of using these imaging techniques to study other neurodegenerative diseases.

“The point of MIND is to have all the researchers in an open lab environment,” said Anne B. Young, the chief of neurology at MGH and the director of MGH-MIND. “When somebody like Brian finds a new way of looking at something like Alzheimer’s disease we can then go quickly to looking at the same issues in other diseases.”

—Staff writer Alissa M. D’Gama can be reached at adgama@fas.harvard.edu