Insulin's role in Alzheimer's

Several large studies have shown that people with diabetes are at especially high risk for Alzheimer's disease.

Steven Arnold, director of the University of Pennsylvania's Memory Center, said diabetics are 50 to 100 percent more likely to get the fatal, memory-destroying disease.

This has made researchers increasingly interested in the role that insulin, the hormone that's out of whack in diabetes, might play in Alzheimer's.

In the brain, Arnold said, insulin is important for cell growth and releasing neurotransmitters that allow cells to communicate. It enhances learning and memory.

Arnold is the senior author of a new study in the Journal of Clinical Investigation that looked at the brains of people with Alzheimer's disease and mild cognitive impairment, often a precursor to dementia. He found insulin resistance in their brains, even though the people did not have diabetes. Arnold said the chemical differences between those who did and did not have memory problems were striking. "I've never seen a difference this large," he said.

When cells are insulin resistant, insulin is present but the cells don't respond as much as they normally would. Insulin resistance is the hallmark of Type 2 diabetes, the kind that 90 percent of American diabetics have. Untreated, it leads to high blood sugar.

Arnold's team studied brain samples taken from people who had died. Even in dead cells, several steps of chemical reactions could be seen. The study found "tremendous abnormalities pretty much all the way down the line" in people with Alzheimer's.

There's no easy way to test brain insulin resistance in the living. Arnold said it's likely that people with diabetes have brain insulin resistance, but others could have it, too.

Many diabetes drugs are designed to lower blood sugar, but some act as insulin sensitizers. Arnold is now seeking funding to test whether one such drug, metformin, can help people with dementia or mild cognitive impairment.

- Stacey Burling