Alzheimer's-Associated Plaques May Have Impact Throughout The Brain

February 27, 2009

Adapted from Massachusetts General Hospital

The impact of the amyloid plaques that appear in the brains of patients with Alzheimer's disease may extend beyond the deposits' effects on neurons—the cells that transmit electrochemical signals throughout the nervous system. In an article in the February 27, 2009 issue of Science, researchers from the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) report that amyloid plaques may also increase the activity of astrocytes, star-shaped nervous system cells traditionally considered to provide a supporting role in normal brain function. They also show that amyloid-induced astrocyte hyperactivity extends throughout the brain rather than being confined to regions directly adjacent to plaques.

"Our work suggests that amyloid plaques might have a more complex role in altering brain function than we had thought," says Kishore Kuchibhotla of MGH-MIND, lead author of the Science article. "Plaques develop rapidly and have been shown to cause relatively acute, localized neuro-toxicity. We show that astrocytes could provide a network mechanism that may stretch the impact of plaques to more distant areas of the brain."

Astrocytes were long considered to provide passive support to neurons, but in the early 1990s it was discovered in cell culture that they also could transmit signals by means of transient increases in calcium levels that move from cell to cell in a wave-like manner. These calcium waves travel relatively long distances in response to a variety of external stimuli. Since astrocytes are so abundant—making up about half the volume of the brain—and found throughout the brain, the MGH investigators hypothesized that their function may also be affected by the presence of amyloid plaques.

"We've only begun to scratch the surface of how plaque deposition impacts astrocyte function," he adds. "One key question will be how increased astrocyte signaling impacts neuronal function, and another will be whether astrocyte activity limits or intensifies plaque deposition."

Brian Bacskai, Ph.D., of MGH-MIND, senior author of the Science report, says, "This study not only provides insight into the role of astrocytic networks in the brain, it also suggests new opportunities to manipulate these networks to treat or prevent Alzheimer's disease as well as other neurological disorders. Further studies of pharmacological compounds that interact with astrocytes may someday lead to potential new therapies."

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