Alzheimer's Club

Mouse 8P205-4 appeared to be an unremarkable rodent as it scampered around its glass cage in the research laboratory.

But there was something going on deep in the brain of 8P205-4 that made it different from most other mice.

"This is a very important mouse," scientist Karen Duff said as she picked up the animal by its tail and allowed it to run up the arm of her white lab coat one morning this month.

Mouse 8P205-4 has Alzheimer's disease.

Duff, a molecular biologist at the Nathan Kline Institute for Psychiatric Research in Orangeburg, has spent the past decade perfecting a method of breeding mice with specific genetic mutations known to lead to Alzheimer's.

The genetically engineered mice allow her and other researchers nationwide to study what happens in the brain when Alzheimer's disease strikes.

"We're trying to replicate the pattern of Alzheimer's disease," she said.

In July, her discoveries earned her an $8 million grant from the National Institute of Neurological Disorders and Stroke for her Alzheimer's research.

Next week, Duff, who also is an associate professor of psychiatry at New York University School of Medicine, will receive the prestigious Potamkin award from the American Academy of Neurology. She will share the $100,000 prize with two other researchers.

"Their work has revolutionized the way we conduct Alzheimer research and drug discovery," John H. Growdon, a Harvard University scientist who helped select the winners, said in a statement released by the Minnesota-based association. "The work of these three individuals warrants recognition in that it will have a direct effect on developing treatments and finding a cure for Alzheimer disease."

Duff and other researchers hope that the genetically engineered rodent and others like it can help shed light on the changes that occur in the human brain leading to Alzheimer's.

Understanding those changes in mice can help find new treatments for the disease in the estimated 4 million people nationwide who develop the disorder, which is marked by progressive loss of memory and cognitive function. The number of people afflicted with the disease is expected to rise to 14 million by 2040 as baby boomers age, according to figures from the national Alzheimer's Association.

Stony Point residents Dennis and Nancy Murphy are among the millions of families nationwide who are learning to live with the ravages of the disease.

Four years ago, when Dennis Murphy was 61, he was diagnosed with the early stages of Alzheimer's.

But because of research like the kind Duff is doing, Murphy is still able to lead a satisfying life. He takes several newly discovered medications that appear to be halting the progression of the disease.

"He drives, he gardens, he sees friends and family," Nancy Murphy said. "We're lucky he had early diagnosis and got early treatment to stave it off."

Scientists have long suspected that two abnormal microscopic proteins in the brain are responsible for the memory loss and deterioration in cognitive functioning that signals Alzheimer's disease. One protein is known as amyloid plaque, which accumulates outside the brain's nerve cells. The second are called "tangles," which are twisted strands of protein that form inside cells.

Mouse 8P205-4 was bred to have a form of Alzheimer's disease caused by a buildup of amyloid plaque in the brain.

Duff has devised a series of experiments to test the cognitive function of that mouse and others.

In one experiment, the mouse is put into a shallow pool of water. The pool has several "arms" or corners equipped with a platform above the water. As part of the experiment, the mice are given clues — a light or a bright color — to help them find the correct arm with the platform.

Mice without Alzheimer's disease are able to find the platform easily and remember where it is.

But mice that are bred to have the disorder are unable to find it.

"They swim around the pool, and they don't know where they are going," Duff said. "It's like a person with Alzheimer's, who can't remember how to get home."

Other experiments with the mice are leading to new insights into the development and treatment of Alzheimer's.

Duff, along with researchers at the Mayo Clinic, are experimenting to see if lithium can reduce brain "tangles" that also lead to dementia.

Lithium helped remove the tangles from some of her genetically engineered mice, Duff said. Researchers are now experimenting to see if doses of lithium can reverse dementia in people. "The initial data is good," she said. "It looks very promising."

Source: Jane Lerner. Orangeburg researchers tackle Alzheimer's disease. The Journal News (28 March 2006) [FullText]