Medical Minute 6-24: Mapping Alzheimer's Disease: Medicine's Next Big Thing?

By: Vanessa Welch Email
By: Vanessa Welch Email

These days, James and Birdie Brown enjoy watching TV together, but
college is where their story began.

"Yeah, boy! The sharpest thing on campus."

The night James proposed, he went over to Birdie's dorm window.

"We talked and talked and talked, and I asked her to marry me. She said, 'Are you crazy?' I said I couldn't answer that. I don't know if you tell the truth or not," said James Brown.

The two married and had five children -- all of them doctors.

"That's me, and that's you. I'm a happy mother."

But that didn't save Birdie from Alzheimer's disease.

"I wouldn't accept it. You don't want to believe that this is going down."

When James had a stroke two years ago, the couple moved into this assisted living center.

The Brown's are one of 35-million families living with Alzheimer's worldwide. A new, international initiative could help unravel the disease's mysteries.

"It's been a long time coming."

Doctor Jonathan Haines of Vanderbilt University is part of the global team that will map all the genes involved in Alzheimer's.

"What it allows us to do is to get to the endpoint of understanding what genes are involved and start the process of understanding why these genes are involved," said Jonathan Haines, Ph.D.,
Director, Vanderbilt University's Center for Human Genetics Research.

By comparing the genes of 20-thousand Alzheimer's patients with 20-thousand healthy elderly subjects.

"We should be able to identify ways of slowing or stopping or even potentially preventing the disease from occurring."

For now, James will stick to a promise he made long ago.

"When I stood up and said, 'I do,' it says through sickness and in health."

For more information on other series produced by Ivanhoe Broadcast News contact John Cherry at (407) 691-1500, jcherry@ivanhoe.com.

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MEDICAL BREAKTHROUGHS - RESEARCH SUMMARY:

BACKGROUND: Alzheimer’s disease is the most common form of dementia or memory loss that is serious enough to interfere with daily life. Alzheimer’s disease accounts for 50 percent to 80 percent of dementia cases. There are more than 5.3 million people in the United States with the disease. Alzheimer’s Disease International estimates there are 35.6 million people living with dementia worldwide. Total estimated worldwide costs of dementia were $604 billion in 2010.

Alzheimer’s is a progressive disease where dementia symptoms gradually worsen over the years. It’s the sixth leading cause of death in the United States. Those with Alzheimer’s live an average of eight years after their symptoms begin, but survival can range from four to 20 years. Alzheimer’s is fatal and currently has no cure. Available drugs only marginally affect disease severity.
(SOURCE: Alzheimer’s Association)

RISK FACTORS: The most important risk factors are age (most individuals with Alzheimer’s are over 65), family history and heredity. Scientists know genes are involved in Alzheimer’s. Genetic tests are available for both APOE e4 and the rare genes that directly cause Alzheimer’s. Still, health professionals do not routinely recommend genetic testing for Alzheimer’s.
(SOURCE: Alzheimer’s Association)

MAPPING ALL ALZHEIMER’S GENES: There is now a global collaboration to discover and map all genes relating to Alzheimer’s disease. The collaborative effort is known as the International Genomics of Alzheimer’s Project (IGAP) and will combine the knowledge, staff and resources of four consortia that work on Alzheimer’s disease genes:

• Alzheimer’s Disease Genetics Consortium (ADGC) from the United States
• European Alzheimer’s Disease Initiative (EADI) in France
• Genetic and Environmental Risk in Alzheimer’s Disease (GERAD) from the United Kingdom
• Neurology subgroup of the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE)

IGAP researchers will compare the genetic information of more than 20,000 Alzheimer’s patients with 20,000 healthy elderly subjects. As the study progresses, 10,000 additional people with Alzheimer’s and 10,000 healthy elderly subjects will be added to the study.

FOR MORE INFORMATION, PLEASE CONTACT:
Craig Boerner, National News Director
Vanderbilt University Medical Center
Nashville, TN
Craig.boerner@vanderbilt.edu

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THE FOLLOWING IS AN IN-DEPTH INTERVIEW WITH THE DOCTOR FROM THE STORY ABOVE:

Jonathan Haines, PhD, Director, Vanderbilt University’s Center for Human Genetics Research, discusses the advances made in the detection of genes involved in the development and progression of Alzheimer’s disease.

Can you start of by telling us a little bit about the current project you and your collaborators are involved with?

Dr. Jonathan L. Haines: This is an international project to try to identify all of the genes involved in Alzheimer’s disease, and it has been a long time coming – we have had several consortia (groups of researchers getting together individually (so there is one in the United States, there is one in Britain, as well as one in the rest of Europe) – we are now pulling all of that together into one very large consortium.

It must be pretty exciting for you to have all of these brilliant minds coming together for a greater cause.

Dr. Jonathan L. Haines: It is very exciting to be pulling the best expertise from all of these minds to work together in tackling this very important problem.

How exactly are you going about this when you don’t know for sure someone has Alzheimer’s disease until they have passed away?

Dr. Jonathan L. Haines: What we are actually doing is that we have collected blood samples from well over 20,000 individuals who have Alzheimer’s disease; either they have already passed away and we have now been able to see with the autopsies that they in fact have the classic symptoms of Alzheimer’s disease in the brain or because they have been clinically diagnosed with Alzheimer’s disease. Clinical diagnosis to Alzheimer’s disease is 90 – 95 percent predictive of what you will see once they have passed away.

In due course, you are comparing these 20,000 individuals with Alzheimer’s disease to a large group who are generally cognitively normal; am I correct in saying that?

Dr. Jonathan L. Haines: We are comparing the individuals that have Alzheimer’s disease to a large number of individuals who do not; in general older individuals who are cognitively normal and therefore are a good comparison group.

Can you discuss how exactly this works?

Dr. Jonathan L. Haines: What we do is we take the blood samples, we extract DNA from all of these individuals, and so we are now investigating 50,000 different samples. What we do is characterize a lot of DNA variation along the entire genome in each one of those 50,000 individuals. In our study, what we are looking at is somewhere between 5000,000 and 1,000,000 different variations in each individual person.

It’s almost mindboggling to think about all of that.

Dr. Jonathan L. Haines: It is mindboggling. The advances in technology have really been tremendous, and that is part of the reason that we can now do these kinds of studies. We have so much data that we can generate on each individual.

Can you talk about some of the implications with this because there are so many people that are impacted by this disease?

Dr. Jonathan L. Haines: The implications of this are several. One is that we will learn so much more about exactly why Alzheimer’s disease occurs and what is going on. Despite the fact that we have been researching Alzheimer’s disease since its discovery in the 1900s, we really still do not know all of the stuff that is going on with the disease. We don’t understand what starts the disease and moreover the continuous progression of it. By identifying all of the genes involved, we hope and should be able to obtain a lot more information as to why that process happens. Once we have an understanding as to why that process commences in some individuals, we can try to identify how we can stop some of that from occurring.

Can we cure Alzheimer’s disease?

Dr. Jonathan L. Haines: I don’t think that we will be able to cure Alzheimer’s disease. What I think that we may be able to do is either delay the onset of the disease (we are talking about much older individuals so they may die from other diseases). If we can just advance the onset age maybe 5 – 10 years, then there will be much less of Alzheimer’s disease in the population. We may be able to stop he process early on or keep it going exceptionally slowly so that people have more years being cognitively normal, and they can still maintain their current lifestyle and furthermore have addition years living a normal life.

So you have been working since 1985 on Alzheimer’s disease, is that correct?

Dr. Jonathan L. Haines: Yes.

What have you seen change in those past 25 years or so with our strengthen base of knowledge of the detrimental disease?

Dr. Jonathan L. Haines: The first thing that changed was the realization that genes were in fact important. When I started in 1985, it was not clear that genes were going to be an imperative part of understanding what was going on with Alzheimer’s disease. It is very clear now how important genes are, and with the changes and advances in technology we are now able identify a lot of those genes. It has turned out and our realization has been that the genetics of Alzheimer’s disease is much, much, much more complicated than we originally though and appreciated back in the late 1980s.

For all of the people who have seen Alzheimer’s disease affect their loved ones and moreover fear for themselves later in their lives what they saw that disease do, is there a chance of not going through that kind of cognitive regression?

Dr. Jonathan L. Haines: It is still a concern. What we will not be able to do with all of this genetic information is look at a specific individual and say that you are at a very high risk of developing Alzheimer’s disease or you are at a very low risk of developing Alzheimer’s disease. It is not going to work that way. All of these genes individually have a very small effect on Alzheimer’s disease. Collectively (looking at 20 – 30 different genes), we are still not really going to be able to change the probabilities or predict the probabilities in a very substantial way for any one individual.

What is the hope then behind it all?

Dr. Jonathan L. Haines: The hope is that by understanding these genes, by uncovering all of them, we will be able to understand the process. Once we are able to understand that process, and what is going on in Alzheimer’s disease (more so then we do now), we should be able to identify ways of slowing, stopping, or potentially preventing the disease from occurring.

So there are a lot of different groups involved in this. Can you briefly discuss the magnitude of uncovering the mysteries being Alzheimer’s disease?

Dr. Jonathan L. Haines: The magnitude of this (just in the United States), there are about 40 – 50 different institutions that are involved in our part of the study. That is just in the U.S. – in fact, there are another 20 – 30 in the U.K. and there are an equivalent number in Europe that are involved. So we are talking about hundreds of labs around the world that are working collaboratively to solve this problem.

This has essentially become your life’s work. What does all of this mean for you?

Dr. Jonathan L. Haines: This has absolutely been part of my life’s work, and what it means to me is that we are going to be able to move more rapidly and make more progress because we are all working together and sort of rowing in the same direction. What it allows us to do is get to the end point of understanding what genes are involved and furthermore why these genes are involved.

Do you think that this research offers some kind of hope for a person who’s loved one is suffering from Alzheimer’s disease?

Dr. Jonathan L. Haines:
I think that it does offer hope for a lot of individuals because we are making a lot of progress with Alzheimer’s disease. There is the potential here for creating new drugs that might be able to slow or stop the onset of the disease. There may be other types of interventions (i.e. behavioral interventions) in addition to other types of tasks. There may be potential for types of diets that we don’t currently understand very well that may be able to help people maintain a healthy brain essentially so that they can live longer and better through their late stages of life.

It is just such a terrible disease.

Dr. Jonathan L. Haines: It is. It really is a very difficult disease to deal with especially if you are a caregiver.

I think that in a sense it might be more difficult for the caregivers because these individuals with Alzheimer’s disease don’t fully comprehend what is happening to them.

Dr. Jonathan L. Haines: Well, in the early stages of the disease, the person who is starting to develop the symptoms is clearly aware of what is going on, and it is exceptionally frustrating for them to not be able to do things that they are used to being able to do and they know that is happening. It’s not a completely smooth progression. There are good days and there are bad days. They will have some days where they are doing just fine and have other ones where they are really struggling. They know what is going on so it is really difficult for the people who have Alzheimer’s disease as well. It is difficult for people to see their loved one have more and more difficulty with day to day activities, so they start having to do things for themselves as well as their loved one who is gradually slipping.

Is there anything that we have learned recently that may be contributing to the development as well as progression of Alzheimer’s disease?

Dr. Jonathan L. Haines: Well, what we are learning with this study is how much genetics really has to do with the disease. What we are now learning is that the genetic part of Alzheimer’s disease may interact with the environmental part of Alzheimer’s disease, whether that is your diet or exposure to other things. We don’t yet know, but as we are identifying which genes are involved we can look specifically at interactions between some of the genes in addition to between some of the things that we have thought to be a contributing factor in the past that might be of environmental origin.

So this is going to be an ongoing study until you find the answer?

Dr. Jonathan L. Haines: It is going to take some time. This is going to be an ongoing study for a very long time, which is typical of most research. As soon as you identify something and make a real discovery . . . 10 more questions are going to pop up and further your investigation. There is just so much more to learn after you have that base to grow from. There is still a lot more to do. We are learning a lot but there is a lot more to learn, and hopefully that will help guide us towards being able to slow the progression or perhaps prevent Alzheimer’s disease sometime in the future.

What can you tell us about the genes that you have found thus far, and how they play a part in understanding Alzheimer’s disease?

Dr. Jonathan L. Haines: There could be as many as 50 genes that contribute to Alzheimer’s disease. We are just now learning what some of these genes are, and it looks like they are involved in a lot of the processes of the brain (processing proteins in the brain) but exactly how that works we just don’t know yet. There are several genes that are already known. There are three genes recognized to be involved in the rare form of early onset Alzheimer’s disease, and we have known about those for quite some time. There is one major gene that is involved in late onset Alzheimer’s disease that we helped uncover back in the 1990’s . . . and now there are three additional ones that have been published within the last year that we know about.

What is the advantage of having such a large consortium working on uncovering the mysteries behind Alzheimer’s disease?

Dr. Jonathan L. Haines: One of the real advantages of bringing the consortia together, having this extremely large data set and all of these people working on it is that we can make much more definitive statements about whether that gene is involved or whether that gene is not involved. There have been a lot of studies over the past 20 years looking at individual genes and relatively small data sets, and people will find things that other people just didn’t see. There has been a lot of disagreement (controversy is not the right word) about what is involved and what isn’t. With getting all of these people together and looking at these very large data sets, we can make much more definitive statements about what is involved and what is not involved.


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