Alzheimer Center Study Suggests New Approach to Treatment

Most researchers believe that the death of nerve cells in the brain is the root cause of the dementia and behavioral changes seen in Alzheimer's disease. Until recently, scientists believed that sticky clumps (amyloid plaques) and tangled fibers found in the brains of people with the disease were directly responsible for triggering this death. A new study led by Dr. Karl Herrup, a neuroscientist and director of the University Alzheimer Center, and his colleagues Dr. David Geldmacher, the Center's clinical director, and Dr. Yan Yang, a research fellow, offers a different way to look at the old research. The team found that brain cells can behave in a process similar to cancer and attempt to reproduce themselves with disastrous results. In April, the prestigious Journal of Neuroscience published the results of their study.

"It's an important paper," said Dr. Creighton Phelps, director of the Alzheimer's Disease Centers program at the National Institute on Aging, which helped to fund the research. "We've always been curious why certain cell types are vulnerable to death in Alzheimer's. This study has given us a possible mechanism for why this happens."

"This new study puts a different spin on the 'sticky clump' idea," Dr. Herrup said. "Neurons are highly resistant to division. But what this disease tells us is that you can eventually override the control circuits and drive these cells to divide. They get to make that mistake only once."

Brain cells are programmed never to divide. But in both cancer and Alzheimer's, there seems to be a similar loss of control, with otherwise healthy cells erroneously trying to replicate themselves. The affected brain cells seem to grind to a halt partway through the process of dividing, ending up with a toxic extra copy of genetic material they had intended to give their offspring. Dr. Herrup thinks that having an extra set of 24 chromosomes is such an imbalance that it eventually kills nerve cells and their communication links to nearby neurons. It is a novel explanation for the advancing cell death that causes the losses of Alzheimer's.

The research team examined hundreds of nerve cells from the brains of seven people with Alzheimer's disease and four people without the disease, donated through the autopsy program. They studied neurons from areas of the brain hit hard by the disease, where up to 80 percent of neurons die. The new findings about attempted cell division suggest another treatment approach: finding a way to jam whatever is telling the neurons to try to copy themselves. "We're a long way from a specific treatment," says Herrup, "But every new insight provides a new target for drug development or other therapy. It makes the job of finding a cure for Alzheimer's disease just a little bit easier"

Research Updates

Over the past year there have been many exciting breakthroughs in our understanding of Alzheimer's disease (AD), raising many question:

Q: Is AD more common than in the past?
A: Yes. Only because we recognize it more, through advances in diagnosis. And more people live longer to the age of risk.

Q: What causes AD?
A: Scientists do not yet fully understand what causes AD, but is is clear that AD develops as a result of a complex cascade of events that take place over many years inside the brain. The disease may be triggered by the interaction of different genetic and non-genetic factors in different individuals. Scientists have known for many years that amyloid plaques in the brain are a prominent and diagnostic feature of AD. The second hallmark feature of AD are abnormal collections of twisted threads of a protein called tau, referred to as neurofibrillary tangles.

Q: What are the major risk factors for AD?
A: Age, or getting older in and of itself is the major risk factor for AD. Genetic factors or family history of AD is another know major risk factor. Others include prior head injury and being female. Very recent studies suggest that a high fat diet and inactive lifestyle may increase the risk of AD.

Q: Is aluminum the cause?
A: No. Aluminum can cause a dementia called "dialysis dementia," but it is not AD. The aluminum detected in AD brains is an artifact related to the chemical binding properties of amyloid and aluminum. It is safe to use aluminum utensils.

Q: Mom had AD, should I get "the genetic test?"
A: In general, no. Scientists have identified several mutations in three genes causing early onset AD; the APOE e4 allele of the APOE gene has been identified as a risk factor for late onset disease. However, there is still much work to be done and there is no specific genetic test that is any more informative than the family history.

Q: How can Alzheimer's disease be treated?
A: There are 4 medications approved by the FDA for AD. They all act by inhibiting the breakdown of an important brain chemical messenger, acetylcholine. The first was Cognex^TM; the second was Aricept^TM; the third Exelon^TM; and the newest Reminyl^TM. These drugs do not stop or reverse AD, but they slow the progression of the disease. Other treatment approaches are medications to treat depression, delusions, and agitation. Behavioral management techniques and caregiver skills training are also being used to improve the quality of life for both patients and their families.

Q: What about the new medicine made from daffodils?
A: This is galantamine or Reminyl^TM. It was approved by the FDA this spring. Overall, its effectiveness is similar to Aricept and Exelon, the other agents approved for AD.

Q: Mom had AD, should I take Vitamin E?
A: Vitamin E, an antioxidant, has been shown to slow the rate of AD progression by as much as 25%. It has not, however, been shown to prevent or delay onset. Another antioxidant, gingko biloba, is being studied but results remain inconclusive.

Q: Mom had AD, should I take estrogen and anti-inflammatories?
A: The use of estrogen in women and anti-inflammatories (e.g., ibuprofen, acetaminophen) in both sexes has been associated with a lower risk of developing AD. Neither has been shown to be very effective in altering the course of AD, once established. Research continues in this area and there are no definitive answers yet.

Q: What about the vaccine for Alzheimer's ...when can I get it?
A: The vaccine is still in the experimental phases of development. Researchers have shown that administration of an amyloid vaccine can eliminate formation of plaques in mince. There is still major work to be done in determining whether the vaccine will be safe and effective in humans. Even in the best-case scenario a widespread vaccine for AD will not be available for several years or even longer.

Q: What about gene therapy for AD?
A: In a ground breaking procedure, physicians at the University of California, San Diego, have surgically implanted genetically modified tissue into the brain of a 60-year-old with AD to deliver a brain survival molecule called nerve growth factor to the dying brain cells. The therapy is not expected to cure AD, but it is hoped that it may restore brain cells. Researchers caution that this is an experimental procedure and it may take several years to determine whether it will be a useful therapy.

Autopsy Program Update

The decision for a family to consider a brain autopsy for a loved one is often a difficult one. If you are involved in this decision making process, here are three reasons to consider a brain autopsy that may be helpful in finalizing your decision. First, a brain autopsy is the only way to definitively make a diagnosis of Alzheimer's disease. A clinical diagnosis of Alzheimer's disease is only about 85 percent accurate. Second, having an accurate diagnosis can be beneficial to the children and grandchildren of the individual suffering from this disease. The third reason is hope - the hope that is provided through research in finding causes, treatments, and ultimately a cure for Alzheimer's disease and other dementia's. An autopsy is an educational process for the family members and for researchers. This hope can only become a reality through those who are willing to participate in this educational process which opens doors and provides answers for future generations.

I would like to take this opportunity to introduce myself to those of you who I have not spoken with personally. My name is LaWanda Crawl and I am the Research Operations Manager and Autopsy Coordinator. If your family decides to participate in the program, be assured that you will be assisted throughout the process. May I emphasize that making pre-arrangements will relieve some of the stress that is experienced during bereavement. If you have any questions regarding the autopsy program or require enrollment forms, please contact me by phone at (216)844-6411 or by e-mail at lyc2@po.cwru.edu.

Caregiving Study

The University Alzheimer Center has just begun a new study designed to find out how computers can best be used to provide information and support to persons caring for a family member with memory problems. To conduct this study, Dr. Kathleen Smyth and her research team have developed a computer-based support group for family caregivers called CO-MES. CO-MES stands for "Computer Mediated Support for Family Caregivers," and is also a Latin term meaning fellow traveler, companion on a journey, friend, or comrade. By connecting to CO-MES from their homes, caregivers will be able to

• communicate with other caregivers and with specially trained group leaders;
• ask questions that will be answered by knowledgeable health and social service professionals; and
• have access to up-to-date and reliable information about dealing with dementia.

CO-MES builds on work the Center has been doing in cooperation with the Cleveland Area Alzheimer's Association for many years. The goal of the project is to demonstrate that use of a computer-based support group will benefit family caregivers by giving them opportunities to share with and learn from other family caregivers, to get to know new people, and to experience personal growth and development.

Two different types of computer-based groups will be studied. One type will be lead by a family caregiver of someone with memory problems, and a professional staff member from the Center will lead the other type. Caregivers who do not have their own computers will received one on long-term loan from the project. All caregivers that take part will be asked to answer a short questionnaire seven times over a two-year period so we can find out if they benefit from taking part in the groups. Over the next few months, letters will be sent to participants in the Center's Caregiving Research Program describing the study. Kathy Winter, coordinator for the project will then make a follow-up call to answer any questions and invite caregivers to participate. If you have questions about the study, please call Kathy at (216)844-6415 or 1-800-252-5048 extension 46415.

EIGHTH DAY OF THE WEEK

In April during Minority Health Month, over 700 people attended the free educational drama, EIGHTH DAY OF THE WEEK .

Thanks to the Ohio Commission on Minority Health, Cuyahoga Community College's Center for Applied Gerontology, IJN-1 Foundation Youth Development Institute and Cleveland State University's Black Studies Program for their financial support! Thanks to all the volunteers including staff from the Alzheimer's Association, CSU Black Studies Program and Center staff who helped make this a successful and fun time! Thanks to those who attended and brought their family and friends!

After seeing the play that focuses on a family facing the realities of Alzheimer's disease, many people expressed interest in participating in our research program. If you or someone you know has memory loss significant enough to discuss with a doctor, please give us a call. Our research program may be a resource for you and your family. Current studies include visual studies, medication trials, caregiver studies and discovering risk factors. All research activities are confidential, voluntary, and free of charge. Please give Kathy Shaw or Darlyne Redd a call at 216-844-6400.

The University Alzheimer Center supports a program of outreach and education to African Americans. Its aim is to ensure that African Americans have access to the best possible clinical care, up-to-date information and the full range of research opportunities.

New Resource

Progress Report on Alzheimer's Disease, 2000 highlights recent research conducted and supported by all the Alzheimer's Disease Research Centers funded by the National Institute on Aging (NIA) and other Institutes at the National Institutes of Health (NIH). It is an excellent resource, describing new findings and next steps in the cause of Alzheimer's disease, improving early diagnoses, developing treatments, and supporting caregivers. You can obtain a free copy by calling the Alzheimer's Disease Education and Referral (ADEAR) Center at 1-800-438-4380 or http://www.alzheimers.org.

Tips for Healthy Aging

The past year has been filled with many studies about healthy brain aging. They provide support that a healthy lifestyle, with good dietary habits, exercise, social support and a positive attitude may protect us from brain disorders such as Alzheimer's disease. For example, a recent study found that a positive outlook on life might fight off Alzheimer's disease and make you live longer. We know that regular exercise helps to keep a healthy cardiovascular system, controls weight, and keep muscles healthy. What is less common knowledge are the benefits of exercise for the brain. Exercise can improve blood flow to the brain, elevate mood by stimulating the release of certain brain chemicals, and releasing stress and tension. Staying active physically, mentally and socially can help your brain and may help to fight off Alzheimer's disease.