Neuroscientist Receives $1 Million Alzheimer's Research Award

November 17, 1999

A University of Rochester neuroscientist who has been at the forefront of research on Alzheimer's disease for more than 20 years has been awarded $1 million by the Alzheimer's Association to continue his studies.

Paul Coleman, Ph.D., is one of three recipients of the Alzheimer Association's Pioneer Award for Alzheimer's Disease Research. The other two are Linda Teri, Ph.D., of the University of Washington in Seattle, and Dennis J. Selkoe, M.D., of Brigham and Women's Hospital in Boston. Each will receive $1 million in research funding over the next five years.

Coleman first turned his attention toward Alzheimer's 20 years ago, and his work on the basic biology of the disease is recognized worldwide as central to the development of better diagnostic tests and treatment. Recent work by Coleman and his research group could form the basis for a simple test that may one day tell healthy people whether they are in the earliest stages of the disease.

Today, by the time a person is diagnosed with the disease, more than half of his or her cells in some parts of the brain have died, leading to symptoms like memory loss, agitation, and child-like behavior known so well to caregivers. Several studies have indicated that the disease may be affecting the brain years or decades before symptoms become noticeable-indeed, one German study showed very early Alzheimer's-like changes in the brains of some people who had died in their 20s. Currently the only way to diagnose the disease in a patient is from the presence of symptoms, which are evident only after many brain cells have already died.

"We know the disease has been working its mischief in the brain for decades before somebody starts to notice symptoms and goes to a physician and gets diagnosed," says Coleman, a professor at the Center on Aging and Developmental Biology at the University of Rochester Medical Center. "The fact that the disease develops for perhaps 50 years before it becomes a serious problem for patients presents a wonderful window of opportunity for diagnosis and treatment.

"We want to be able to detect the disease before there are symptoms, then stop or slow its progression sufficiently so that the person can live out his or her normal life span without ever showing symptoms."

Coleman and other scientists have long wondered how sick and healthy cells can be interspersed throughout the brains of the 4 million people in the United States who have the disease. Understanding why some brain cells die while others nearby thrive may be the key to understanding the disease itself, Coleman says. The technology the team developed last year allows scientists to study brain cells in unprecedented detail by simultaneously measuring the activity of several genes in a single cell, to see which genes are turned on and which are dormant. They've looked at a few dozen genes thus far, and they plan soon to look at the activity of 20,000 genes from a single cell simultaneously.

Early studies indicate that some of the same genes involved in cancer may also play a role in Alzheimer's disease. Cancer cells grow and divide uncontrollably, eventually pushing aside healthy cells. Coleman's team of 12 students and professors has found that the activity of some of the same genes involved in cancer differs dramatically between healthy and sick cells in Alzheimer's disease. It's possible that a nerve cell is erroneously trying to divide, Coleman says, and the brain tries to "protect" itself by attacking the cell.

The current research came about when Coleman decided in the late 1980s, four decades into his career, to learn more about the burgeoning field of molecular biology: He spent two summers at Cold Spring Harbor Laboratory learning new laboratory techniques. In one class, says Coleman, the teacher handed him a piece of brain from a rat and asked Coleman to analyze the genes within it. "I said, 'Of course, but I want you to know that it violates my aesthetic sensibilities to take this piece of brain in which I know there are so many different kinds of cells, and grind it all up together, and then try to learn anything from it,'" Coleman says.

Thus was born a collaboration between the teacher, Jim Eberwine of the University of Pennsylvania, and Coleman; together they developed the new technique to look at gene activity within a single brain cell.

Taking on new questions has been a consistent theme throughout Coleman's career. He had spent years studying the way the healthy brain works when he and a student decided one day to take a detailed look at brain tissue damaged by Alzheimer's disease. The 1979 work was among the first to show precisely what happens in the brains of patients who have the disease. The team found that individual nerve cells in the human brain continue to grow as a healthy person gets older, but not as Alzheimer's patients age. "We interpreted this to mean that the normal and healthy aging human brain retains significant ability to make new connections and learn new things, and that Alzheimer's disease is at least in part a loss of this ability," he says.

In addition to his own research, Coleman for the last 10 years has headed one of the world's leading Alzheimer's centers. The University of Rochester Alzheimer's Disease Center is one of 28 such centers in the nation funded by the National Institutes of Health; through the center, physicians and scientists perform basic research and provide care and support to patients and their families. Coleman is also editor of the journal Neurobiology of Aging, the leading journal where scientists discuss new findings on aging and the brain. The recipient of many honors, Coleman is one of only 12 researchers nationwide who have received the NIH Leadership and Excellence in Alzheimer's Disease (LEAD) award.

Coleman received his undergraduate degree from Tufts University and his Ph.D. in psychology, with a concentration in studies of the nervous system, at the University of Rochester. He served on the faculty of Tufts University, Johns Hopkins University and the University of Maryland before joining the University of Rochester in 1967.

University of Rochester Alzheimer's Disease Center

The University of Rochester's Alzheimer's Disease Center is dedicated to improving the lives of Alzheimer's patients and their caregivers through research, clinical care, and education. The center, one of 28 funded by the National Institute on Aging, brings together more than 75 basic scientists, physicians, nurses, and others throughout the Medical Center and Strong Memorial Hospital to work together to diagnose, treat, and prevent the disease. In Rochester the center is known as the site of treatment for most Rochester-area residents with the disease; nationally its researchers are known for their contributions to our understanding to all facets of the disease, from basic biology to patient care.

Through the center, medications are available that may reverse some symptoms and slow the onset of others. Other forms of treatment can help with a wide range of behavioral and emotional changes such as aggression, depression and insomnia. Options include physical therapy, occupational therapy, speech therapy, and counseling for patients and their loved ones.

The center also provides patients and families with information needed to cope with an Alzheimer's diagnosis: what the disease and prognosis mean, local and national resources, opportunities to participate in clinical trials, and links to other health care providers. Support and information is available through the Rochester Chapter of the Alzheimer's Association, the Lifetime Wellness Program at Monroe Community Hospital, the Alzheimer's Disease Assistance Center, and other programs.

A multi-disciplinary approach to caring for people with dementia is the cornerstone of patient care. A team of neurologists, psychiatrists, neuropsychologists, and nurses provide evaluation and treatment at satellite locations as well as at two main clinics, the Cognitive and Behavioral Neurology Clinic at Strong Memorial Hospital and the Geriatric Neurology and Psychiatry Clinic at Monroe Community Hospital. The clinics serve more than 850 Rochester-area patients with the disease.

The center also conducts a large number of research studies aimed at better understanding the cause of Alzheimer's disease and identifying new treatments. Among current efforts or recent studies at the center and in other areas of the University of Rochester Medical Center:

· A project to develop a simple, convenient test to detect the disease before symptoms appear, opening the door to protecting brain cells before they die.

· More than a dozen studies testing the effectiveness of new medications. Through these studies, Rochester residents have access to new treatments far earlier than most Alzheimer's patients nationwide. Last year, physicians found that drugs used to treat epilepsy appear to soothe the agitation of Alzheimer's patients. One current study is checking whether a drug known as a cox-2 inhibitor, sometimes referred to as a "super aspirin," can help prevent the disease.

· Extensive studies by researchers in the School of Nursing to help improve the quality of lives of Alzheimer's patients and their families. Researchers have found that rocking-chair therapy and humor both help patients feel less distressed and agitated.

· A project to learn more about the "motion blindness" that one team discovered many Alzheimer's patients have; it's a big reason why some patients become disoriented. Physicians are studying whether the finding makes it possible to pinpoint which patients will encounter serious difficulty driving or getting around their neighborhoods. That would allow some patients to live independently longer than they otherwise might while alerting other families that they should be extra vigilant in keeping tabs on their relatives.

· Research to take advantage of a highly sophisticated technology that scientists have developed to turn on or off genes in the nervous systems of mice. The work opens up a new area of research, allowing scientists to check if memory and learning in patients might someday be enhanced using gene technology.

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