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Research Patient Care

Dr. Potter: Progress toward new Alzheimer's treatments

In podcast he says the disease is ‘not just a health problem, but a societal problem’

Author Chris Casey | Publish Date September 24, 2019

Huntington Potter, PhD, has spent his career researching the manifold mysteries of Alzheimer’s disease, which currently affects over 5.5 million people in the United States at a cost of about $200 billion a year. By 2050, almost 14 million Americans are expected to be living with the disease at a cost of $1 trillion a year – in Medicare and Medicaid costs alone.

“This is a major, major problem,” said Potter, professor of neurology in the University of Colorado School of Medicine. “It’s not just a health problem, but a societal problem.”

In conjunction with World Alzheimer’s Month, Potter sat down with CU Anschutz 360 for a candid discussion about the state of Alzheimer’s research and progress being made toward possible treatments. He notes that the center he directs, The Rocky Mountain Alzheimer’s Disease Center, is now one of the major Alzheimer’s research centers in the country.

On this episode of CU Anschutz 360, you’ll hear about:

  • Current strides toward finding treatments, including a CU Anschutz-led clinical trial that is showing promising early results;
  • The possible benefits of drinking coffee and other dietary habits that might help reduce a person’s risk of getting Alzheimer’s;
  • The connection between Alzheimer’s disease and rheumatoid arthritis;
  • The connection between Alzheimer’s and Down syndrome, which is the focus of the Linda Crnic Institute for Down Syndrome, of which Dr. Potter is also a member;
  • How Alzheimer’s is actually a disease of middle age; and
  • Potter’s personal interest in the illness, which is the sixth-most common cause of death in the United States.

When Potter came to the CU Anschutz Medical Campus seven years ago, Denver was one of the last major metropolitan areas in the nation without an Alzheimer’s research center. He was specifically recruited to launch a center, and the clinical and research enterprise has grown from a single neurologist seeing about 100 patients a year to a staff of 50 physicians and researchers seeing almost 3,000 patients a year.

Many aspects of the disease remain mysterious – such as how diet and exercise might reduce the possibility of getting Alzheimer’s, how inflammation plays a role in the illness, and exactly why amyloid deposits in the brain cause nerve cells to die – and it will take the collective work of researchers worldwide to develop treatments or a cure, Potter said.

Potter&CaseyINS2
Dr. Huntington Potter chats with Chris Casey in the Office of Communications. 

“Alzheimer’s is an equal-opportunity killer; we’re all at risk,” he said. “If we live to be 85, almost half of us will have Alzheimer’s disease. It’s not as though one ethnic group or another is protected or guaranteed to get it. We’re all in the same boat, and we all have to bail like mad and fix the leaks.”

When asked what advice he gives to people diagnosed with Alzheimer’s as well as their caregivers, Potter said, “I recommend that the most important thing is to not lose heart … many scientists around the world are trying their best to develop new treatments.”

 

Episode Transcript

[Music]

Chris Casey Welcome to CU Anschutz 360, a podcast about the CU Anschutz Medical Campus. We feature faculty staff and students on our campus and their interesting and innovative work. Hello. I'm Chris Casey managing editor in the Office of Communications.

Chris Casey Today, let's introduce you to Dr. Huntington Potter, professor of neurology in the School of Medicine, and Director of the Rocky Mountain Alzheimer's Disease Center.

[Music fades]

Chris Casey Well, Dr. Huntington Potter, thank you for taking some time out to visit with us here today. This being World Alzheimer's Month, we thought it would be an appropriate time to discuss some of the research going on around Alzheimer's and just talk about the disease in general and what we know about it.

So, first of all, could you just tell me - what is Alzheimer's disease, and how does a person get it?

Huntington Potter Well, Alzheimer's disease is one of the diseases that can cause dementia. So first thing we have to get clear is that dementia is a clinical description of a disorder, but Alzheimer's disease is the most common way to get dementia if you're elderly. So that's why they are sometimes used interchangeably.

Chris Casey Hmm.

Huntington Potter But, we should stick with either Alzheimer's disease or other neurodegenerative diseases.

Chris Casey Okay. And about how many people a year get Alzheimer's disease, and how many currently have it?

Huntington Potter Well, currently there are about 5.5 to 6 million people with Alzheimer's disease in the United States. It's the sixth most common cause of death - certainly among the elderly. And the total number of people who get Alzheimer's disease, I think is about one every 45 seconds in the United States. So it's pretty common.

Chris Casey Wow. And could you explain a little bit about how you became personally interested in studying Alzheimer's? Was somebody in your family affected by it?

Huntington Potter Well, we actually don't know. My grandfather on my father's side died at about 85 with dementia, but he had enough other health problems. So it could have been Alzheimer's, could have been something else. We never knew, but that wasn't what got me excited. What got me excited was that Alzheimer's is probably the most important neurological disease. It is a biochemical disease. It is a genetic disease, and all of those were areas of my interest in education. So it fit perfectly into what I should be doing.

Chris Casey And how is it that you chose to come to the University of Colorado Anschutz Medical Campus to pursue your research into the disease?

Huntington Potter When I first was looking for a move out of Florida for various reasons, I had started an Alzheimer's center there and things had changed - the recession had come and I was looking for a new opportunity. And so, I was recruited to the Department of Neurology to start an Alzheimer's center and looked forward to it because it was a new opportunity, something to build from scratch. It was perfectly the kind of thing I like to do.

Chris Casey Great. And could you describe maybe a profile of somebody who might be more likely to get Alzheimer's disease? For example, would, gender or lifestyle play into somebody's...[Crosstalk]

Huntington Potter ...Risk.

Chris Casey ...Yes, risk for it?

Huntington Potter Yes. That's a very good question. Unfortunately, women are at a higher risk of developing Alzheimer's disease compared to men. It's not because they live longer, although they do, and that increases the risk. Because age by itself is the greatest risk factor for developing Alzheimer's disease. But apparently, that loss of estrogen at menopause, possibly their lifestyle. We don't really know why women are at higher risk. African Americans are at higher risk. Hispanics are at higher risk, but not perhaps as much as one might think. since sometimes their risk factors, such as cardiovascular problems, are suggestive of a much higher risk than they actually exhibit.

But I would say that the best thing to remember is that Alzheimer's is an equal opportunity killer. We're all at risk. If we live to be 85, almost half of us will have Alzheimer's disease. And it's not as though one ethnic group or another is protected or guaranteed to get it. We're all in the same boat and we all have to bail like mad and fix the leaks.

Chris Casey What about exercise or smoking? Do they play any roles?

Huntington Potter A very good question. Smoking increases the risk of Alzheimer's about two-fold. Exercise can reduce it maybe 25 or 30%. We usually say that, uh, you can't do very much about your genetics, but you can do something about your lifestyle. And exercise, exercise, exercise - is good. Not only for your heart, which you've been told for a long time, but also for your brain.

Chris Casey And there was a recent article in The New York Times about weightlifting and how weight training appears to promote the creation of new neurons and maybe memory centers in the brain. Is there anything to that?

Huntington Potter Well, the kind of exercise that is most beneficial for Alzheimer's is still under investigation. For a long time, it was thought that some kind of exercise that increases your cardiovascular output was probably better. But now, some new research suggests that there may be other kinds of exercise which would be good too. I think the jury is out yet. We have more research to do.

Chris Casey And how about the relationship of diet and Alzheimer's? We've heard anecdotally perhaps, how coffee or maybe fish oil added to a diet, can maybe have beneficial results.

Huntington Potter Yeah. That's a good question and is the subject of a lot of research right now. We did some work early on with mice that get Alzheimer's disease. They have a genetic human mutation that has been taken from a family that has inherited Alzheimer's disease. Now the mice get Alzheimer's disease. When we fed the mice caffeine, their cognition got better. In fact, it returned to that of a perfectly normal mouse. If we look at the epidemiology, it seems that people who, in middle age, drink three to five cups of coffee a day, are at about 60% reduced risk of developing Alzheimer's.

But the problem with those kinds of epidemiological studies is that the people who in middle age drink three to five cups of coffee a day are professors, and chief executive officers of companies, and they have many other features that may protect them from Alzheimer's. But we have to do an experiment, and the mice were ideal. We haven't extended that to people because, you can imagine that taking a group of people who drink coffee every day and telling you half of them they have to stop...

Chris Casey (Laughs)

Huntington Potter (Laughs)... is gonna require some convincing. And taking people who don't drink any coffee and asking half of them to start drinking three to five cups of coffee a day, is also difficult. So I don't think coffee is going to be the solution, but it does indicate that your environment and your diet may have an effect. And certainly, the diets that are recommended for good cardiovascular health, the mind diet, the Mediterranean diet, the dash diet. Basically these are vegetables and fruits and olive oil rather than animal-based fats. Plus exercise probably does help. And for now, it's the only thing we can do.

Chris Casey Talk a bit more about the research going on into Alzheimer's. For example, what have we learned about the disease? Such as, what are the 'known unknowns' that you and your team are seeking answers to?

Huntington Potter I think the team of Alzheimer's researchers is really worldwide. We all talk to each other and we all exchange our results and think about what to do. In general, the pathology in the brain, which are these Brillo pads or little amyloid deposits, and the tangles, which are killing nerve cells, - they're universal in the Alzheimer's disease brain. And they definitely cause the problems of nerve cell death and dementia. What we don't know is exactly why they cause nerve cells to die, and that's one of the things that we're trying to find out.

We also don't know exactly how early we're going to have to intervene, because plaques in the brain probably occur 20 years before the first clinical symptoms. And tangles, at least five years. So that means Alzheimer's disease is not really a disease of the aged, it's a disease of middle age, which is only manifest later. So it's very likely we're gonna have to develop interventions, drugs, that can be started at the age of 50 after you've given a blood test and somebody says, "Gee, you look at risk." And then we would take that drug or that treatment for the rest of our lives, as a prevention. Trying to cure it after you already have it, that's gonna be much more difficult.

Chris Casey And, you've alluded to this already, but inflammation is a hot topic in the world of Alzheimer's research. Is inflammation in the brain leading to some of this destruction of neurons?

Huntington Potter Yes, it is. And in fact, if there was no inflammation in the brain, we probably wouldn't get Alzheimer's disease. We can treat mice in ways that reduce the inflammation in the brain. And especially, inflammatory proteins like apolipoprotein E or antichymotrypsin. These are proteins that have a natural function, but they help Alzheimer's disease progress. And without them, we would not have Alzheimer's disease. Now, unfortunately, we can't get rid of those proteins. They have a normal function and they're very important, but it tells us how to potentially develop new drugs. We have to keep them from working on Alzheimer's disease.

Chris Casey You mentioned new drugs - you're currently engaged in a clinical trial of a drug called Leukine. And I understand that, that could be targeting neuroinflammation. Could you talk about how that clinical trial is going and what, what that drug is designed to do?

 

Huntington Potter That's a very good question. We are in the middle of the trial for Leukine, or I should say at the tail end of it - for our first pilot trial. And it's looking promising in two ways. It's not dangerous to people, as far as we can tell. They've had no ill effects, and our report last year at the meetings suggested that our preliminary evidence indicates that people may be getting a little bit better in one test of cognition.

Those data are encouraging, but they basically are encouraging us to do a longer trial, which we will be starting in a couple of months. Now, the way that drug was found is that people with rheumatoid arthritis tend not to get Alzheimer's disease. They're protected, maybe eight-fold. And that's an inflammatory disease, as you know, so we thought, "Well, maybe the body is producing an anti-inflammatory molecule or is reacting to the rheumatoid arthritis in some way that accidentally, inhibits Alzheimer's disease from developing in the brains of these people."

So we went looking, and Tim Boyd and I found many such possible explanations. But we found that a protein called GMCSF may be the reason why people with rheumatoid arthritis are protected. It's increased in the blood of these people and when we injected it into the mice, the mice got immediately better. So that was the source of the clinical trial because that drug is a known human drug called Leukine. It's not used for Alzheimer's disease until we tried it, but it's used to stimulate the bone marrow to make more white blood cells of a special kind called macrophages and granulocytes. And these are like little Pac-Men. They go around the body and they eat up things that aren't supposed to be there, like bacteria and viruses and amyloid deposits.

Chris Casey And also, what is the connection between Alzheimer's disease and Down syndrome?

Huntington Potter Everyone who has Down syndrome develops Alzheimer's disease pathology in the brain by the time they're 30 or 40 years old. The reason for that is that they carry three copies of chromosome number 21 in every cell of their body from conception, and chromosome 21 carries the Alzheimer's gene. So all of us have two copies. They have three copies and they started making those amyloid plaques in their teenage years. By the time they're 35 or so, their brains, if they should die and donate them to science, look like a 70, 80-year-old Alzheimer's patient. And most of them are demented by the time they're 60. So it's very sad for them and for their families, but they're a great gift to science and to all of us, including them, if they help us develop drugs for Alzheimer's disease.

Chris Casey And, here at the Anschutz Campus, you lead the Rocky Mountain Alzheimer's Disease Center. How has that evolved into a leading regional research center? And what kinds of specialists do you employ there?

Huntington Potter When I came, seven years ago, we had one neurologist seeing about a hundred people a year. Since then we've grown in the clinical realm and in the research realm, both clinical research and laboratory research so that we have probably 50 people or so at various stages of research in Alzheimer's disease now. And the clinic sees almost 3,000 people a year. So that's grown, and that's grown thanks to philanthropy, some grants, the university. And we are now one of the major Alzheimer's research centers in the country, with a lot of work and a lot of dedication from many people.

Chris Casey What advice, given that the disease is always fatal, what advice do you give people who are diagnosed with the disease? As well as the important aspect of advice to family members who are going to take on a pretty considerable burden as caregivers?

Huntington Potter That's a very good question. And unfortunately, the answer is different for every patient and every caregiver. Everyone goes through the disease at a different rate. Everyone has different side effects of the disease, and I recommend that the most important thing is to not lose heart. Life is still good, the parts of it that you can enjoy. Remember, from a caregiver's point of view, if your family member is acting out, is causing problems, stress comes, it's not them who's talking anymore, it's the disease. And patience, patience, patience is important.

And get help as soon as you can. Trying to do it all on your own is very, very difficult. And as I say, don't lose heart. A lot of scientists all over the world are trying their best to develop new treatments. And I'm sure that, if it's not Leukine or it's not Leukine alone, it will be something like it that attacks the inflammation in the brain, that attacks the amyloid deposits, and may have to be used in combination, as we found for many diseases. A single silver bullet is probably not in the offing, but that's why we have to talk to each other and share our ideas and our research so that we can come up with the best combination treatment in the next few years.

Chris Casey And as you say, all this collaboration requires I'm sure considerable resources and just cooperation and strategizing. What do you see as the biggest obstacles to finding a cure or new treatments for Alzheimer's?

Huntington Potter That's a good question, and I would say that it is two major things. A general lack of resources, which is slowly changing. Philanthropists have really built the Alzheimer's center here at CU, along with the university. The NIH has finally convinced Congress, with a lot of help from the Alzheimer's Association and all of us researchers, and of course, the people with Alzheimer's disease, that this is a problem that we absolutely have to solve. We'll go broke, otherwise.

The expectation is that if there are no treatments, that the cost for Alzheimer's disease to the nation would be about $1 trillion a year by 2050. So this is a major, major problem, not just a health problem, but a societal problem. That's recognized now. I would say the other problem is that we really took for granted that understanding the mechanism of Alzheimer's disease was automatically gonna give us a treatment, a cure. And it's just turned out to be more complicated than we thought.

And also, it was realized, only in the last five years or so, that we may need to start as early as 10 or 20 years before clinical symptoms in order to have a really major effect on the disease. And that's gonna take special clinical trials and special efforts. So we're all working together, we're doing our best, and we really appreciate the support of the community.

Chris Casey Well, Dr. Potter, thanks for sharing all this very important information. And we appreciate and we're very grateful to have you here and your team doing their work. So thank you.

Huntington Potter It's a pleasure. It's always a pleasure to talk to you.

Chris Casey Thanks.

Disclaimer: Transcripts are generated using a combination of speech recognition software and human transcribers. It may contain minor differences from the audio, including some edits for clarity in print. Please check the recording and with the Communications team before quoting in print. 

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