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Alzheimer's Research Takes a New Turn

Study suggests that gummed-up synapses -- not plaque -- may be at the root of aging brain diseases

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Barres now hypothesizes that diseases such as Alzheimer's might develop if the C1q that has accumulated on the synapses triggers an immune system attack against them.

"The first regions of the brain to show a dramatic increase in C1q are places like the hippocampus and substantia nigra, the precise brain regions most vulnerable to neurodegenerative diseases like Alzheimer's and Parkinson's disease, respectively," Barres said. Another region affected early on, the piriform cortex, is associated with the sense of smell, whose loss often heralds the onset of neurodegenerative disease.

"Our findings may well explain the long-mysterious vulnerability specifically of the aging brain to neurodegenerative disease," he said. "Kids don't get Alzheimer's or Parkinson's," Barres pointed out.

"Profound activation of the complement cascade, associated with massive synapse loss, is the cardinal feature of Alzheimer's disease and many other neurodegenerative disorders. People have thought this was because synapse loss triggers inflammation. But our findings here suggest that activation of the complement cascade is driving synapse loss, not the other way around," Barres explained.

Heather Snyder, director of medical and scientific operations for the Alzheimer's Association, said the new study "adds to the body of information that looks at how the immune system might work in Alzheimer's disease." She added that there are many hypotheses that need to be explored about what may be happening in Alzheimer's.

Noting that much of the research in the current study involved mice, Snyder said future studies need to focus on how C1q affects human brains.

"This is really opening the door that this should be explored further," she said. "It needs to be replicated in the laboratory and also correlated to what it may mean in human beings."

More than 5 million Americans have Alzheimer's disease, and that number is expected to rise significantly as the baby boom generation ages.

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