Calcium’s possible role in Alzheimer’s

A new study in mice finds that plaques associated with Alzheimer’s wreak havoc on calcium’s role in cell signaling.

Careful journalists write that Alzheimer’s disease is associated with the characteristic plaques in patients’ brains, never that it’s caused by those plaques.

Scientists have been uncertain whether these plaques actually cause the memory impairment typical of the disease, but new research on mice suggests that calcium could link the plaques to nerve-cell dysfunction.

“It’s the first evidence that calcium can be affected by [plaques] in areas that are important for synapse formation and learning and memory,” comments Alzheimer’s disease expert Kim Green of the University of California, Irvine, who cowrote a review article published with the new research in the July 31 Neuron.

“Apparently the calcium is playing a very, very important role,” comments Bharat Aggarwal, an expert in cell signaling and inflammation at the University of Texas M.D. Anderson Cancer Center in Houston. The research “provides us more targets for finding treatments for the disease.”

Calcium ions, positively charged calcium atoms, relay signals that control many functions within cells and between neighboring cells. Previous research suggested that calcium might be involved in Alzheimer’s disease, but scientists didn’t have any evidence from living animals.

In the new experiments, Brian Bacskai and his colleagues at Massachusetts General Hospital in Charlestown, Mass. compared two kinds of mice having Alzheimer’s-like conditions to healthy mice. Calcium in the brains of healthy mice was tightly controlled, but plaques in diseased mice elevated the levels of calcium in nerve cells, Bacskai’s team found. Nerve cells closest to the plaques were the most affected.

The researchers also looked at the effects of this calcium imbalance on the cells’ functioning. High calcium levels caused the “wires” between neurons to become malformed, the scientists report.

“The neuron is still alive, it’s just not communicating effectively, which could lead to the cognitive impairment,” Green says.

Abnormal calcium levels might also disrupt the creation of synapses, the tiny gaps across which neuron wires communicate. Forming new synapses is one way that scientists think neurons store new memories.

“There’s little doubt that calcium can change what synapses can do,” comments George Augustine, an expert on calcium signaling in neurons at Duke University Medical Center in Durham, N.C.

However, the new research does not show how the plaques raise calcium levels in the nearby neurons. And scientists don't yet know whether this calcium link in mouse brains also exists in people with the disease.

Found in: Body & Brain and Genes & Cells