Common enzyme interaction could hold clues to Alzheimer’s

McGill University researchers have identified a key two-part process in normal brain development that could shed new light on what causes some people to develop Alzheimer’s disease. Their findings appear in the March issue of Journal of Biological Chemistry.

Dr. Hemant Paudel, an associate professor of medicine at McGill and Alzheimer’s researcher at the Lady Davis Institute for Medical Research at the Jewish General Hospital, led a three-person team that used gene-modified mice and brain cell cultures in search of clues to the origins of Alzheimer’s.

They found that an enzyme called cyclin-dependent protein kinase 5 inhibits the activity of another enzyme called protein phosphatase 1. Both enzymes contribute to the functioning of the so-called tau protein. Tau protein has the potential to cause neuropathological tangles observed post-mortem in the brains of patients who had Alzheimer’s disease.

“Because one enzyme blocks the other, it’s similar to when a ruptured water pipe leaks into a basement with a blocked drain,” explained Dr. Paudel. “This raises questions such as, ‘Can we close the tap and unblock the drain – or, in the case of our research, can we induce tangles in the cell and if so, can we stop them from developing?’”

The brain-wasting disease currently affects an estimated 300,000 Canadians over the age of 65, according to the Alzheimer Society of Canada. “Alzheimer’s costs the Canadian government about $6 billion a year to treat,” said Dr. Paudel. “Not knowing what causes it makes it difficult to treat but this discovery gives us a model to work on.”

Dr. Paudel has been working on this research with collaborator Dr. Lorraine Chalifour and post-doctoral fellow Dr. Tong Li for the past three years, having earlier discovered precisely what roles the two enzymes play in tau protein action.

On the Web: jbc online