The Principal Investigator

The protein garbage (a.k.a. amyloid plaques) that disrupts the normal function of neurons in Alzheimer’s disease also pollutes the abundant support cells of the brain, creating a global disturbance that was previously unrecognized, according to a study in today’s (2.27.09) issue of the journal Science.

Scientists say the findings suggest plaques might have a “more complex role in altering the brain function than previously thought” and may offer new directions for treatment of what’s currently an irreversible and deadly disease.

“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,” Brian Bacskai, of Massachusetts General Institute of Neurodegenerative Disease, said in a news release. Bacskai was the senior author of the Science article.

More than 5 million Americans are living with Alzheimer’s disease – a number that is expected to grow rapidly as America’s baby boomers grow older, according to a 2008 report by the Alzheimer’s Association.

Once regarded as the wallflowers of the brain that passively support the chattering neurons as they form memories and respond to daily stimuli, in the early 90s scientists discovered astrocytes had a few tricks up their sleeves. Just like neurons communicate via electrochemical signals, the researchers found astrocytes transmit long-distance calcium signals in response to stimuli.

Previous studies have shown that the protein plaques in close proximity to neurons is a recipe for neuronal disaster, often leading neurons to die, but researchers were less sure about the effects, if any, plaques had on astrocytes.

The team of researchers used two different imaging techniques and small-molecule calcium dye to probe the astrocytes in the brains of mice genetically altered to develop Alzheimer’s plaques as they aged.

The researchers found higher resting levels of calcium in the network of astrocytes regardless of the proximity to plaque compared to normal mice. Additional imaging revealed stronger and more spontaneous astrocytic signaling in mice with plaques compared to the mutants that had not yet developed plaques and normal mice.

The team then blocked all neuronal activity to determine whether neurons adjacent to plaques were causing the global distribution of astrocytic hyperactivity and found the activity of astrocytes remained unchanged.

“We’ve only begun to scratch the surface of how plaque deposition impacts astrocytes function,” said lead author Kishore Kuchibhotla, in a news release. “One key question will be how increased astrocyte signaling impacts neuronal function, and another will be whether astrocytes activity limits or intensifies plaque deposition.”

Related links:

Alzheimer’s Plaques More Complex Than Thought (U.S. News & World Report, 2.26.09)

Research reveals some of Alzheimer’s secrets (Reuters, 2.26.09)

State’s Alzheimer’s cases to nearly double by 2030 (The San Diego Union Tribune, 2.26.09)