UIC scientists 'ecstatic' about Alzheimer's breakthrough

A group of scientists at the University of Illinois at Chicago's College of Medicine has used a human gene in mice to more accurately measure the damage caused by Alzheimer's disease.

This breakthrough means that researchers will be able to do a better job of studying the full effects of the gene, known as apoE4, on the brain and ultimately develop medications to lessen the harm to Alzheimer's patients, said Mary Jo LaDu, associate professor of anatomy and cell biology at UIC and the research project's principal investigator.

"We identified markers of Alzheimer's disease really early in mice, with new tools. It's like finding the holy grail," said LaDu, who added that she's "ecstatic" about the results.

The presence of the apoE4 gene in the brain significantly increases the risk of developing Alzheimer's disease because the gene does a poor job of clearing out a protein called oligomeric amyloid-beta that scientists believe is toxic to the brain, she said.

"The earlier you can find soluble oligomeric amyloid-beta (in the brain), the earlier you can identify who you're going to want to treat" for Alzheimer's disease, LaDu said. Her team's research was published online last month in the Journal of Biological Chemistry.

The study involved three strains of mice, which all made large amounts of amyloid-beta. Each strain of mouse had the human form of the gene apoE, in one of three versions: apoE2, apoE3 or apoE4.

ApoE2 reduces the risk of getting Alzheimer's disease, apoE3 has a neutral effect, and apoE4 increases the risk of Alzheimer's by 15 times, LaDu said.

"The important thing with Alzheimer's disease is that apoE4 binds and clears oligomeric amyloid-beta poorly. We think that apoE3 and apoE2 are very good at binding and making oligomeric amyloid-beta nontoxic. ApoE4 is not as good at that," LaDu said. "We accidentally created a very good preclinical model … to see what we would see in human models. Human apoE is too important a player in the process to ignore."

The researchers will further study the interactions between oligomeric amyloid-beta and the apoE4 gene, LaDu said.

"The oligomeric amyloid-beta and apoE4 are doing something, or not doing something, to cause the disease. Previously, it was hard to measure oligomeric amyloid-beta. We made an antibody that recognizes amyloid-beta and allows us to measure the oligomeric amyloid-beta. We couldn't measure it before."

David Teplow, a neurology professor at the University of California at Los Angeles, called the study "great, very helpful to the field."

"In previous animal models, the initial disease stages were not observable," he said. "The nice thing about these mice models is that they give time to look at the early stages. It's a very nice model, including the primary risk factor and a tractable system for looking at the development of the disease and the efficacy of drugs that might be used in humans. The model gets us closer to knowing what's going in humans."

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