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Overproduction of brain chemical during early stages of Alzheimer's contributes to memory loss in patients

Rush University Medical Center

Overproduction of the brain chemical galanin during the early stages of Alzheimer's may have an negative effect on the brain and contribute to the cognitive decline of patients, according to a study published in the March 20 issue of Proceeding of the National Academy of Sciences. Researchers from Rush Presbyterian-St. Luke's Medical Center in Chicago, the University of Washington School of Medicine, and the National Institutes of Mental Health studied transgenic (mutated) mice with excessive amounts of galanin to better understand why people with Alzheimer's disease lose their memory.

The study reports the human body may be detecting the underlying pathology of Alzheimer's and trying to rescue deteriorating brain cells with increased expression of galanin. Very early on in the disease, galanin might even be having beneficial effects. As the brain attempts to rescue itself with galanin and the disease progresses, the overexpression of galanin may become its own problem.

This excess of galanin may contribute to the cognitive decline that Alzheimer's patients and their families so dread.

The mice appear to move normally but have problems performing tasks that require them to remember where visual cues were located and had poor memory recall of scent and food odors. Scientists suggest these studies mirror memory loss in people suffering from Alzheimer's.

Researcher Elliott J. Mufson, Ph.D, professor in the department of Neurological Sciences at Rush Presbyterian-St. Luke's Medical Center in Chicago, is an expert in neurochemical pathology of Alzheimer's and studies the deterioration of cholinergic (nerve fibers/nerve endings) neurons.

Mufson examined the brains of the transgenic mice and found that they have 70 percent fewer cholinergic neurons in the horizontal limb of the diagonal band of Broca, similar to what happens in humans with Alzheimer's.

"These mice are a model of at least part of the Alzheimer's syndrome. Now that we have this model, we can study the effects of the overexposure of galanin and how to block it. A drug that blocked galanin might be able to slow or reverse the mental damage caused by the disease.

Because Alzheimer's is so complicated, it may be that someday people have to take a whole cocktail of drugs, such as anti-amyloids, galanin antagonists and anti-cholinesterases," Mufson said.

Co-author Dr. Jacqueline N. Crawley, from the National Institutes of Mental Health, believes "If galanin is playing a role in the disease, then what we know as Alzheimer's could be the result of many parallel events that themselves create complications.

The combination of cell death and inhibitory actions of galanin may be responsible for the memory losses that leaves Alzheimer's patients unable to care for themselves." Galanin's appearance during Alzheimer's is mysterious. Alzheimer's is associated with degeneration of the brain and of cognitive function. People with Alzheimer's have fewer brain cells and reduced amounts of some important neurotransmitters. However, there is no shortage of the neurotransmitter galanin. Autopsies show that people with Alzheimer's have twice as much galanin in certain areas of the brain as peers who die of something else. In Alzheimer's disease, excess galanin appears in the frontal cortex and surrounding the dying cholinergic neurons so characteristic of Alzheimer's. About 4 million Americans have Alzheimer's disease.


Rush-Presbyterian-St. Luke's Medical Center includes the 809-bed Presbyterian-St. Luke's Hospital; 154-bed Johnston R. Bowman Health Center for the Elderly; Rush University (Rush Medical College, College of Nursing, College of Health Sciences and Graduate College); and seven Rush Institutes providing diagnosis, treatment and research into leading health problems. The medical center is the tertiary hub of the Rush System for Health, a comprehensive healthcare system capable of serving about two million people through its outpatient facilities and five member hospitals.

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