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Drug's effect on Alzheimer's may depend on severity of disease
Date:7/16/2014

A cancer drug that has shown promise against Alzheimer's disease in mice and has begun early clinical trials has yielded perplexing results in a novel mouse model of AD that mimics the genetics and pathology of the human disease more closely than any other animal model.

The drug, bexarotene, was found to reduce levels of the neurotoxic protein amyloid-beta in experimental mice with late-stage Alzheimer's but to increase levels during early stages of disease.

The finding, by researchers at the University of Illinois at Chicago College of Medicine, was reported July 16 at the Alzheimer's Association International Conference in Copenhagen by Mary Jo LaDu, who in 2012 developed a transgenic mouse that is now regarded as the best animal model of the human disease. That experimental mouse carries a human gene that confers on people a 15-fold elevated risk of developing AD, making it the most important known genetic risk factor for the disease.

Alzheimer's disease is the most common form of dementia, affecting more than five million Americans. The disease is progressive and eventually fatal. One of the hallmarks of AD is the appearance of dense plaques in the brain composed of clumps of amyloid-beta. But recent research indicates that smaller, soluble forms of amyloid-beta -- rather than the solid plaques -- are responsible for the death of nerve cells that leads to cognitive decline.

Humans carry a gene for a protein in cells called apolipoprotein E, which helps clear amyloid-beta from the brain by binding to it and breaking it down. LaDu's mice carry the most unfortunate variant in humans, called APOE4, or APOE3, which is neutral for AD risk.

"APOE4 is the greatest genetic risk factor for Alzheimer's disease," said LaDu, who is professor of anatomy and cell biology at UIC. "Our previous work showed that compared to APOE3, the apolipoprotein produced by the APOE4 gene does not bind well to amyloid-beta and so does not clear the neurotoxin from th
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Contact: Sharon Parmet
sparmet@uic.edu
312-413-2695
University of Illinois at Chicago
Source:Eurekalert

Page: 1 2

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