Sticky clumps of protein called amyloid usually get the blame for causing Alzheimer's disease. But the real culprit may be calcium, according to a pair of studies published in the research journals Cell and Neuron.
"These two papers together will force everyone in the Alzheimer's field to put the calcium hypothesis much more on the map than it has been," says Kevin Foskett of the University of Pennsylvania, who is an author on both studies.
"This begins to suggest that calcium may be something we can't afford to ignore," says Sam Gandy, chairman of the national Medical and Scientific Advisory Council of the Alzheimer's Association and an Alzheimer's researcher at Mount Sinai School of Medicine in New York.
The new studies look at the connection between Alzheimer's and the way brain cells regulate the amount of calcium they contain.
In order to stay healthy, brain cells need to maintain just the right amount of calcium at any given moment. That depends on the cells responding to signals from elsewhere in the brain.
Foskett and others say an abnormal response to these signals leads to abnormal calcium levels in brain cells, which ultimately leads to Alzheimer's.
One of the new studies appears to confirm the link between calcium and Alzheimer's. It identifies a gene linked to both Alzheimer's and the calcium balance in brain cells.
Researchers found that people who carry one copy of the gene are at least 44 percent more likely to develop the disease.
The study's lead author, Philippe Marambaud of Albert Einstein Medical College in New York, says scientists have been able to discover which chemicals in the brain are produced by the gene.
"So we have potentially not only identified a new risk factor, but also a gene product that could be targeted for drug discovery and therapy," Marambaud says.
He says future drugs might be designed to correct abnormal calcium levels in brain cells. So far, efforts to treat Alzheimer's have focused on preventing or eliminating the buildup of amyloid.
The second study suggests how an imbalance in calcium might actually cause Alzheimer's.
Researchers looked at brain cells from people who have a rare, inherited form of the disease that can strike before the age of 40. They found that these people carry genes that not only cause amyloid buildup, but also problems with calcium regulation.
And the researchers found that when calcium regulation went awry, brain cells produced more amyloid.
Gandy of the Alzheimer's Association says this suggests a new way of looking at an old disease.
"It seems that calcium and amyloid have a sort of hand-and-glove relationship," Gandy says. "So one can cause the other and they can begin a vicious cycle that we think can lead to the disease."