Autopsy Program Update
Adrienne Schaffer

A brain autopsy remains the only accurate way to ultimately determine the reason for a person's dementia. It also adds valuable knowledge to the research process, especially if the person with memory loss has been a participant in our program. Arranging an autopsy is far easier on the family when paperwork is completed ahead of time. By filling out four forms, the procedure will proceed smoothly and save stress on the family.

Steps To Be Completed Now:

• Fill out the Autopsy Permit and Release of Deceased Patient Form. Keep them with your important papers. OR If the registry participant is in a nursing home or other facility, keep the papers in the person's chart at the nursing home.
• Fill out the Family Request for Brain Autopsy and Release of Autopsy, and mail or fax them to me at 216-844-6446.
• I'll call the nursing home and funeral home that you designate, explain our procedures, and send them letters, explaining our program. These letters will be on file and available when needed.

At The Time of Death:

• If the person with memory loss is in a nursing home, a member of the staff will call the funeral director. Otherwise a family member needs to call the funeral director.
• The funeral director will make arrangements with the mortician's office or hospital security staff if the mortician's office is closed.
• The funeral home provides the transportation and bills the Alzheimer Center.

As you can see, the funeral director plays a key role. Once he or she is identified, the burden on the family is minimized.

Four to Six Months after the Autopsy:

• A feedback session is held with Dr. David Geldmacher, our Clinical Director. The session can be by telephone or in person. Often several generations of family members attend the sessions.
• During the session, the autopsy report is explained in detail, a diagnosis is confirmed, and the family has an opportunity to ask any questions.
• The autopsy report is sent or given to the family and a physician if you designate one on the Release of Information Form.

To date, 85 families have had an autopsy facilitated through our program, and another 120 families currently plan to have one.

We welcome your participation in the autopsy program. For questions, forms, or help filling out forms, please call me at 216-844-6411, 8:30-4:30 daily, or leave a message 24 hours a day.

Change in autopsy hours-The mortician's office at University Hospitals is no longer open 24 hours a day. New office hours are 7 a.m. to 7 p.m. weekdays and 7 a.m. to noon Saturdays. This means that some autopsies will no longer be done the same day, but will be completed the morning after. If the death occurs when the mortician's office is closed, the funeral director will transport the deceased to the hospital. In the morning, the funeral director will be called to come back to the hospital. We will pay for both trips. Since the autopsy is scheduled for the morning, there will be minimal delay in planning calling hours or the funeral.

Many of you have inquired about the impact of any delay on the quality of the information we are able to obtain from autopsy. The potential delay of several hours does not detract at all from our ability to provide a definitive pathological diagnosis of the cause of the person's dementia. In addition, delays will have little impact on our research studies of anatomic changes associated with Alzheimer's disease.

Ten Tips for Healthy Aging

1. Eat a balanced diet, including five helpings of fruits and vegetables a day.
2. Exercise regularly. Check with a doctor before starting an exercise program.
3. Get regular health check-ups.
4. Don't smoke. It is never too late to stop.
5. Practice safety habits at home to prevent falls and fractures. Always wear your seatbelt in a car.
6. Stay in contact with family and friends. Stay active through work, play and community.
7. Avoid overexposure to the sun and the cold.
8. If you drink alcohol, moderation is the key. When you drink, let someone else drive.
9. Keep personal and financial records in order to simplify budgeting and investing. Plan long-term housing and money needs.
10. Keep a positive attitude toward life. Do things that make you happy.

Alheimer's Disease in the News

Dr. David Geldmacher, the Alzheimer Center's Clinical Director, responds to recent stories in the news about Alheimer's disease research.

Headline: Researchers Are Working on a New Treatment - that May Stop the Effects of Alzheimer's Disease. (NBC Nightly News, November 15, 1999)

Summary: Dr. Mark Tuszynski and other researchers at the University of California, San Diego, have studied the brains of monkeys that were equivalent in age to humans aged 60 to 70. By inserting genes for nerve growth factor (NGF) into the brain, researchers suggest that they were able to stimulate new brain cell growth. Dr. Tuszynski has received approval from the FDA and is recruiting volunteers for the study.

Response: Stimulating nerve cell growth is an important goal, but not in and of itself a cure for Alzheimer's disease. One problem is that toxic effects of amyloid would still be present, and possibly undoing the positive effects of NCF. Perhaps the more important aspect of these studies is their testing of a "gene therapy" approach to Alzheimer's disease.

Headline: "A New Finding in Drug Search for Alzheimer's: Researchers Isolate What May Be a Key to Alzheimer's Drug." (The Wall Street Journal, October 21, 1999)

Summary: Researchers at Amgen Inc. have identified a mysterious and long-sought enzymer that may play a central role in Alzheimer's disease. The Amgen team isolated the enzyme beta-secretase, which causes the tiny protein fragments to build up and clutter the brains of Alzheimer's patients. Many specialists believe Alzheimer's disease is caused by the accumulation of these protein fragments into clusters called amyloid plaques, although the evidence isn't definitive.

Response: Understanding the beta-secretase enzyme is a key step in trying to prevent amyloid deposition in the brain of a person with Alzheimer's disease. The next step after this important study identifying the enzyme is to develop drugs to inhibit its effects. This process is still a long way off from human testing.

Headline: Hope Meets Hype: They Talk about a Breakthrough in Alzheimer's Research, But What Does that Really Mean? Time, July 19, 1999

Summary: Writer Christine Gorman reacts to media coverage when Elan Pharmaceuticals, a biotech company headquartered in Ireland, reported they had produced a vaccine that could prevent plaques from forming and dissolve existing ones in the brains of mice. The researchers speculated that a similar approach might be used to treat people. When Ms. Gorman read the article in the journal Nature about the study, her reaction was "to negotiate a tightrope between real promise and false hope." Were the media too enthusiastic and overly optimistic about this discovery?

Response: The media today have several masters. The free electronic media (e.g. broadcast TV and radio) in particular are enslaved (via the share rating system) to advertisers. When they report on a story - particularly one with broad public health concerns like Alheimer's disease - they are strongly influenced by its likelihood to attract viewers. Medical research is incremental by its very nature, i.e., the steps are small. It is much more akin to compound interest than winning the lottery. Remebering that helps keep these reports in context.

Research Discoveries Open New Paths

Karl Herrup, PhD

Two new developments in Alzheimer's disease research have been announced recently. Both have important implications for developing new treatments that could one day allow doctors to stop the progression of the disease in its tracks.

The first development was the announcement that immunization of laboratory animal models of Alzheimer's disease prevents the accumulation of the toxic brain deposits, or plaques, that are believed to be a major contributor to the disease. This finding raises the hope that a vaccine for Alzheimer's disease might one day be possible. Alzheimer's disease plaques are deposits of a waxy-like substance known as beta-amyloid. Alois Alzheimer was the first to discover the association of a clinical dementia with plaques and mentioned them in his 1907 description of the disease. They are still the chief criterion that the pathologist uses to make a definite diagnosis of Alzheimer's disease.

In recent years, specific strains of laboratory mice have been engineered to replicate various features of Alzheimer's disease in an experimental animal. The behavioral symptoms of the aged mouse models are difficult to equate with the human condition, but the brains of these animals regularly develop plaque deposits as they age. Last summer, researchers at Elan Pharmaceuticals announced that they were able to block the appearance of plaques by immunizing the animals with beta-amyloid itself.

The result caught the research world somewhat by surprise since antibodies raised in the blood are rarely effective against targets located exclusively in the brain. The published findings were impressive, however, and they have been enthusiastically received. Needless to say, therapies based on this finding are many years away; but the approach is a novel one and is being actively pursued.

One major caution in considering these results is that the mouse is at best an imperfect model of the human disease. The study of the basic disease biology is always informative, but the translation of the finding in mice to therapies in humans often requires some adjustments. The issue of safety is also important. The entire set of consequences of large scale immunizations against a naturally occurring body substance cannot be predicted in advance and caution is advisable.

The second important development in the Alzheimer's field during the past few months was the announcement of the discovery of the enzyme that produces the beta-amyloid protein itself. The small toxic beta-amyloid peptide is derived from a much larger precursor protein by an abnormal digestion orchestrated by an enzyme called the beta-secretase. This elusive enzyme was well known only by its activity; no group had been able to locate the protein until this past fall. Now three separate laboratories have reported the isolation of a protease (a protein cutting enzyme) with all the properties expected of the beta-secretase. The newly identified protein belongs to a novel group of enzymes that are found in many types of tissues in addition to the brain. Given this wide distribution, most researchers believe that the production of beta-amyloid by this enzyme is a perversion of its normal role in the body; however, what this normal function might be remains a mystery. The discovery is an important one because the more we can learn about the beta-secretase, the more likely it is that we will be able to develop a drug that will block its action and prevent the production of beta-amyloid. Clinical trials in humans are not likely to begin in the immediate future since we need to learn more about the normal function of the enzyme and the consequences to the body of blocking its function.

Both of these discoveries are important steps in Alzheimer's disease research. Each opens a new and unsuspected avenue for therapy and cure. Both are being followed up by teams of scientists from around the world and will almost undoubtedly lead to new and more advanced treatments. Stay tuned!!

Kudos to Dr. Geldmacher!!

David Geldmacher, MD, Clinical Director/Director of Clinical Trials at the University Alzheimer Center has been selected to be included in the biographical directory published by Marquis Who's Who®, the leading biographical reference publisher of the highest achievers and contributors from across the country and around the world.

Dr. Geldmacher will be profiled in the 2000 edition of Who's Who in America, which will be available in October 2000. Who's Who is an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world.