Alzheimer's Plaques More Complex Than Thought

27 feb 2009-- The impact of amyloid plaques in the brains of people with Alzheimer's disease may be more complex than believed, U.S. researchers report.

It was already known that amyloid plaques affect neurons. But the researchers at the MassGeneral Institute for Neurodegenerative Disease in Boston found that amyloid plaques may also increase the activity of astrocytes, nervous system cells that play a supporting role in brain function. This astrocyte hyperactivity isn't confined to regions directly beside the plaques, but extends throughout the brain.

The findings appear in the Feb. 27 issue of Science.

"Our work suggests that amyloid plaques might have a more complex role in altering brain function than we had thought," study author Kishore Kuchibhotla said in a hospital news release. "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."

Since astrocytes make up about half the volume of the brain, Kuchibhotla and colleagues wanted to determine if astrocyte function may be affected by amyloid plaques. They used imaging techniques that gave them a real-time view of brain cell activity in living mice.

The researchers found that astrocytes flicker on and off at a much higher rate in mice genetically altered to have an abundance of brain plaques than in those without plaques. The plaque-associated astrocyte activity appeared to be synchronized and traveled to distant areas of the brain in a wave-like fashion.

Using another type of imaging technology, the researchers also found that mice with plaques had higher-than-normal resting calcium levels throughout their astrocyte network. Astrocyte activity wasn't reduced when the researchers blocked the activity of neurons. This indicates that the known impact of amyloid plaques on neurons isn't responsible for increased astrocyte activity.

"This is the first clear evidence in a live animal model that amyloid plaques perturb calcium signaling across the astrocyte network via a neuron-independent mechanism," Kuchibhotla said. "It has been suggested that these intercellular calcium waves, which previously had been observed only in response to some sort of external stimulus, indicate the existence of, or response to, a traumatic insult. Our data support this hypothesis, but whether the calcium signals we observed actually protect or harm cells remains to be determined."

"One key question will be how increased astrocyte signaling impacts neuronal function, and another will be whether astrocyte activity limits or intensifies plaque deposition," Kuchibhotla added.