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Dr. Jones: What if anyone, man or woman, young or old, could make eggs out of skin cells and have an unlimited and easy to access source of baby making? How could that happen? This is Dr. Kirtly Jones from Obstetrics and Gynecology at University of Utah Healthcare and this is In-Vitro Gametogenesis on The Scope.

Announcer: Covering all aspects of women's health, this is the Seven Domains of Women's Health with Dr. Kirtly Jones on The Scope.

Dr. Jones: The holy grail of regenerative medicine is to be able to make organs or tissues that need replacing, think cartilage in your sore knees, from cells that are yours and are easy to get. In the process of human development, cells that are very early in the embryo are called totipotent. That means they can turn into any cell in the body. The time that cells are totipotent in normal human development is quite short, maybe just a few days after fertilization. After that, cells start going down a pathway of development and cannot go back. Cells become pluripotent meaning they can turn into a number of cell types of one type, perhaps the cells of the tissues of internal organs but they cannot make eggs or sperms anymore.

When you hear the word stem cells or stem cell research, it refers to cells that are not completely developed or differentiated into skin or hair or other tissues but can be turned on in natural development to replace cells in certain tissues when those cells die. Over the past 30 years, a lot of research has been focused on harvesting and growing stem cells to be used in treatment of disease. The poster child is bone marrow transplantation for the development of blood cancers like leukemia. This treatment is highly effective in using blood stem cells from cord blood or an adult's bone marrow or maybe someone's own blood stem cells to replace the diseased blood cells.

Okay. Although it isn't prime time or covered by insurance, some clinics are harvesting stem cells from tissues and injecting them into knees that have had the cartilage wear down in hopes that these stem cells will decide to make cartilage when they find themselves in the right place.

So what about eggs? What if you could take skin cells, just a little bit of skin tissue, and harvest the stem cells that help replace skin cells, turn back the developmental clock to make early egg cells? In the ovary, there is a supply of egg cells that are being very early in development and can grow and mature to ovulate each month when a girl goes through puberty until they run out at menopause.

Recently, a Japanese research group did just that in mice. They took mouse skin cells, turned back the developmental clock and made early egg cells, let the eggs develop, added sperm, made embryos, put them in a mouse, and made mouse babies. Okay. This is where what is called the yuck factor comes in. The yuck factor is when someone hears about a new development in science or medicine and it tweaks their emotional or moral sense. Think face transplants. There is a little yuck factor there. Sometimes the yuck factor calms down with a little more understanding and experience.

The possibility of making animals or humans this way to have a source of gamete cells, meaning eggs and sperm, available to men or women, young or old, sort of tweaks the yuck factor in some folks. Many people experience the yuck factor when the first in-vitro fertilization baby was born or when human egg donation became a way for postmenopausal women to bear children or when human embryo banks were established with frozen embryos to be chosen, bought, and shipped to be transferred into a surrogate uterus. So here we have the yuck factor with the process of growing eggs or sperm in the lab from skin cells or other cells. This is called in vitro gametogenesis, generating gametes in the test tube.

There are some very interesting scientific questions about early development of eggs and sperms and embryos that could be answered using this technology. And people who'd run out of eggs or sperm in the case of women, may be menopause, in the case of men or women, may be chemotherapy, might have their source of eggs and sperm with their own DNA. If a woman and her female partner wanted to make a baby with DNA from both of them, they could use this technology. Of course, although the mice were made in the lab with in vitro gametogenesis this year, that doesn't mean the technology will be available to make human embryos tomorrow.

Like cloning, making an embryo from a skin cell, think Dolly the Sheep, it never really took off for humans, and there are still a lot of questions about the safety for the newborn child to be, but it may be right around the corner and what will we do about that? Stay tuned and thanks for joining us on The Scope.

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Interviewer: Aging on a microscopic scale, up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Adam Hughes, Assistant Professor of Biochemistry at the University of Utah. Dr. Hughes, when I think of aging, I think about getting wrinkles, going gray, slowing down, but you think of aging on a different scale. How do you think about aging?

Dr. Hughes: We think about aging, I'd say, more at an organismal level or even more specifically than that, the cell biology level. Sort of looking at not how aging affects the whole organism, but how it affects specific structures within our cells within different tissues.

Interviewer: A lot of your research focuses on one component of the cell, an organelle called the mitochondria. First of all, can you orient us to the mitochondria? What does it do?

Dr. Hughes: Sure. Mitochondria, they're known as the powerhouse of the cell. Historically, they're drawn as kidney-bean-shaped structures you see in all the textbooks, but mitochondria do a lot of different things in metabolism. They're a double-membraned structure that produces lipids, they're involved in oxidative phosphorylation, they basically make energy for cells and also participate in a large number of metabolic reactions.

Interviewer: Studying the mitochondria is actually a whole field in and of itself. What's some of the evidence that mitochondria is involved in aging?

Dr. Hughes: Mitochondria has drawn a lot of attention, not only for its role in changes in mitochondrial function affecting how long an organism lives but it's also become very clear that as mitochondria become faulty with age, which happens for a number of different reasons in a number of contexts, this is also been linked to driving the development of a large number of age-associated disorders as well.

Interviewer: And as it turns out, there's quite an elaborate system for getting rid of or repairing mitochondria that does not function well. You've just published some research about this in the journal "eLife."

Dr. Hughes: I haven't explained much of what we've been doing. We've been using yeast as a model system to understand the aging process. So it's pretty cool that the single-celled eukaryote, the simplest one, and a lot of labs have been using it for a very long time to understand lifespan regulation type processes. And so our lab actually uses this organism in it does, in fact, age. A yeast cell, we measure aging by the number of times a cell can divide before it dies. Now, it happens about 30 times before a cell dies. And so in these old cells, it started several years ago when I was a postdoc at the hutch in Dan Gotchling's lab, we found it in old cells there was damaged or dysfunctional mitochondria.

So we decided to use this system to try to see what we can learn about how cells handle this, how they respond, what can they do. And we went into it, at the time, wondering if we could model pathways that were already known in mammals, one of the most prominent being the autophagy-dependent or self-eating pathways that had already been fairly well characterized. And so when we went into this, we set out to see in an old cell, do we see pieces of mitochondria? And we're visualizing all this on the microscope, being ripped off and degraded after they're damaged/

And we saw that there was, in fact, this going on in old yeast cells and so we initially thought it was similar to what had been observed already. And that's how we got into it. We didn't go into it looking for new pathways, but eventually it sort of, as we got more into the details of what this is going on, we realized they totally new type of quality control that we discovered that was different than anything else that had been described before.

Interviewer: So what is it? What did you find and how is it different from what was there, what you knew before?

Dr. Hughes: In general, in this field, it was always thought as a mitochondria became damaged that these systems aren't very smart for a lack of a better word, that they would go to the damaged mitochondria and just degrade the entire thing. Which seems a bit wasteful and so when we came into this we thought the same thing and we were using a protein on the mitochondria. We are monitoring it by microscopy and we could see that it was being eaten. But what we did that went beyond these original studies and other systems was there are about 1000 different proteins in the mitochondria. And we just started looking at other ones too. So most of the studies in mammalian cells had only looked at one or two and made conclusions.

And so we went on and looked at all mitochondrial proteins to see how they were all being degraded. What we discovered, based on this, and this is the big crux of this study, is that the pathway we've uncovered now is the concept and idea that mitochondria actually, under these situations when they're damaged, don't just get totally degraded as a whole. They can actually be broken down piece by piece. And what I mean by that is certain proteins can be basically selectively sorted out and removed from the mitochondria and degraded and the rest of it can be left intact.

Interviewer: Do you have any ideas yet of whether this pathway relates to aging or how it relates to aging?

Dr. Hughes: We got into it looking at aging, but we think it's actually going to have many applications in other systems, especially sort of metabolic-related disorders. We've been working from the standpoint of seeing the structure and it forms, it's sort of very descriptive. It forms, it gets released, it gets degraded and certain proteins go into it and certain ones don't. But understanding what the importance of it is and why it happens has been a much more difficult question. And we are starting to get at that.

We didn't get into a lot of it in this currently published paper, but some of our certain experiments are directed in the range of one thing that we did include here. And one big clue to us is the identity of the proteins that are actually degraded by the system. So again, the mitochondria has about 1000 proteins in yeast and when we looked at the proteins that are degraded by the system that we discovered, it's only about 10% of those proteins. And it turns out it's very selective for one particular group, which is a group of proteins called the mitochondrial nutrient carrier protein.

So the role of this group of proteins, there are about 30 of them, in the in the mitochondria, they basically facilitate the transport of all nutrients into and out of the mitochondria. So we're working from the fact that these are the main targets of this pathway and we think that giving us a big clue as to what might be its role. And so clearly, they're metabolite transporters. They're very heavily involved in all aspects of metabolism. And so we're testing the idea now, a hypothesis that this pathway may be very important for actually protecting mitochondria in times of changes in cellular metabolic state.

Interviewer: It's also kind of amazing to me that, especially in something as simple as a yeast, that there are still entire processes that we're still discovering.

Dr. Hughes: Yeah, I think that's definitely a really cool point. Sometimes, yeast in this day and age will get a bad rap. You hear all kinds of things that yeast research is done and things that we used to only be able to do in yeast, now we can do them in humans and other organisms. But what's sort of the big arena right now, I'd say, in the yeast field is cell biology. And it's been very limiting for a long time, the ability to look at all different proteins and all different things within the cell.

And what's really cool in the yeast field is that many, many years ago now, probably 10 years ago, a lab developed a collection of all yeast proteins tagged with a fluorescent protein, GFP. So it's about 6000 proteins in yeast. And so we have strains that contain every single one of them. And so there are a number of labs across the country, including ours, that are essentially using this collection to look at how the entire protium changes not in terms of levels, but in terms of localizations in cells.

And people are discovering a lot of new things that no one had ever noticed simply because we have the tools to do it now. And this is what's really nice in yeast. And we still don't have the ability to do this in mammalian systems yet. So I think the future will get there and we'll be able to start looking at these. But there's a lot of new, I'd say, cellular structures, cellular compartments that form under very particular conditions that people just hadn't seen before.

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Interviewer: A different way of thinking about how cancer starts. Up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on the scope.

Interviewer: I'm talking with Dr. Charlie Murtaugh. Professor of Human Genetics at the University of Utah and with Nathan Krah. They've just published a paper in the journal "E-Life."

Dr. Murtaugh, as far as I understand it, your results really kind of put the initiation of cancer in a different light.

Dr. Murtaugh: The standard model for how cancer starts is that you have a cell that accumulates a bunch of different mutations until that cell becomes sufficiently abnormal that it turns into a cancer cell and stops behaving like a normal cell. And we were interested in how that applied in pancreatic cancer. And we and others have found that the genetic mutations that occur in pancreatic cancer in the model that we use are not enough to actually trigger the beginning of the disease. So we knew there's something else had to be going on. And what we think is going on now is that the differentiation state of the cell.

So how the cell knows what it normally is supposed to do. In this, case the cells are cells that make digestive enzymes to break down food. And they are normally focused 100% on that task. They're not really dividing. But then, a change happens and those cells forget what they're supposed to do and then in that context then those mutations that can cause cancer can become hyperactive and the cells start to become transformed and move toward cancer.

Interviewer: Nathan, maybe you can tell me why you're focusing on pancreatic cancer in the first place.

Nathan: Yeah definitely. So pancreatic cancer is one of the deadliest solid tumors that patients can have. It has one of the poor survival rates of just about any cancer with a five-year survival of only about 5%. So really, any clues that we can get that push toward earlier detection or better treatment options would be good.

Interviewer: You're implying principles of development to understand cancer. What does that mean exactly?

Dr. Murtaugh: Right. I have a long-standing interest in the process of differentiation. This maybe does go back 20 years. So it just how cells learn to adopt the mature fates that they're supposed to achieve, starting in the embryo and the differentiation continues in the adults. So, of course, we are continually shedding skin so we have to differentiate new skin all the time, new hair, etcetera. And it was through studies of differentiation in the pancreas and trying to understand how the different cell types, the endocrine and exocrine cells, how they get to differentiate that we began to be interested in how that might apply in cancer.

Because it seemed, based on classical work, that it was possible. That in fact cancer might start from not only genetic mutations that we know are important, but changes that are non-genetic like loss of differentiation.

Interviewer: So kind of the ideas that when a cell is differentiated, it's mature and is thought to be just sort of fixed that way, kind of stable that way. And so if you disrupt that, things go wrong?

Dr. Murtaugh: Yeah, exactly. Exactly.

Interviewer: And how did you move that into the cancer paradigm? I think you've been researching a gene, PTF1, for a while?

Dr. Murtaugh: Right. So PTF1 is a gene that's called a transcription factor. And transcription factors are proteins that regulate other genes. So a lot of what differentiation involves is turning on expression of genes that are important for the carrying out the function of the cells. So, for example, the exocrine cells that we study, they make hundreds of digestive enzymes. Like huge concentrations.

And so what PTF1A does normally, in a mature cell, is it activates those genes. So without PTF1A during development, you can never make the cells that normally digest food. And what we found is that once you are a mature cell you still require PTF1A in order to continue making those enzymes and in order to repress alternative choices.

So cells tend to not like to do nothing. If you take away a factor like PTF1A that forces them into a specific identity, if you take that away they will kind of cast around and look for an alternative identity. And in a healthy cell, that might not be a big deal. And in fact, we find that just taking PTF1A away is not enough to cause cancer.

But in a cell that has an underlying cancer-causing mutation, when the cell starts trying to change its mind about what it's supposed to do, those mutations can kind of express themselves and then the cell very, very quickly becomes abnormal.

Interviewer: You've done these experiments in an environment where there's already something wrong? And so this is like one more step that breaks the camel's back?

Dr. Murtaugh: Yeah, exactly.

Interviewer: Nathan, what do you see when you do that?

Nathan: When we take away PTF1A in the context of cancer-causing genes or oncogenes, we see that these cells are rapidly transformed into pre-cancerous lesions. And what's really interesting is that if we just express these oncogenes or cancer-causing genes alone, that's really not sufficient to do too much. They occasionally form these pre-cancerous lesions, but in the context that PTF1A loss, almost every cell that loses PTF1A will give rise to cancer.

Interviewer: And is there any indication that this happens in human pancreatic cancer?

Dr. Murtaugh: Right. So that's a really good question. So one of the things that we were able to show is that in fact in the lesions of humans, these early stage precancerous lesions, the PTF1A is also being shut down. And in fact, there are some other studies out there that didn't focus on PTF1A, but have all sort of implied the same thing that this must be happening at a very early stage in cancer. And so it does look like it probably does happen to humans and one of the things we're really interested in going forward is sort of doing the reverse, which is if we could turn it back on in human cells, would we be able to stop the cancerous cells from growing.

Interviewer: Right. I mean, will that point to a different kind of therapy?

Dr. Murtaugh: I think so. I mean, most cancer therapies in pancreatic and other cancers are targeted to cell division. And, of course, that's what conventional chemotherapy does and it has limitations because it can kill the normal dividing cells. And there are other therapies that are targeted at the mutated signals that occur in the cancer and in some cases like lung cancer, those have been really effective therapies. But in pancreatic cancer, it's been very challenging to do that. So the oncogene, the cancer-causing mutation that is so central to pancreatic cancer is one that is in a protein that is very hard to make drugs against.

And so this has been a long-standing problem in the field. But we do feel that differentiation is something that there's almost no disadvantage. In theory, at least, there are no side effects from having too much differentiation in the pancreas because it's an organ that is normally very differentiated. So if there were a way to reactivate the normal differentiation of these cells, that by itself shouldn't have any major side effects. And the question is whether it would be effective as a therapy.

Interviewer: Yeah, fascinating. I mean, is there any indication that this happens in other cancers as well?

Nathan: Yeah, that's a really good question. So one thing I think that's exciting to us is if we really look throughout the GI tract, there are a lot of cancers that undergo this process called metaplasia or a change in cell fate, which almost always precedes cancer and is usually associated with chronic inflammation.

And so one good example is in the esophagus, a lot of people have the acid reflex and that can lead to changes in the cell populations in the lower esophagus. And it's thought that those changes are actually necessary for cancer formation. And so we show a very similar story in the pancreas. We think that this actually a broadly applicable principle where you need a loss of differentiation in order to actually initiate cancer.

Announcer: Interesting, informative, and all in the name of better health. This is the Scope Health Sciences Radio.

Interviewer: New insights into how cancer cells gain the deadly power to grow uncontrollably up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Jared Rutter Professor at The University of Utah. Dr. Rutter you've published a report, "Molecular Cell," describing what could be a key change that takes place in cancer cells that gives them an advantage over the normal cells in the body. I think what's fascinating about your discovery is that it relates to a hypothesis that was posed early last century. First of all, can you explain what this hypothesis is, The Warburg Effect?

Dr. Rutter: Dr. Warburg discovered that cancer cells do a different kind of metabolism than normal cells. That fundamental observation has been born out repeatedly in the years since and now has become a very active area of research both in discovery based research and academia, as well as more applied research going on in companies trying to treat cancer. The question will be whether that can now be exploited and in treatment.

Interviewer: You can tell me if I have this right, in a normal cell sugars or carbohydrates eventually go down a pathway where the cells powerhouse, mitochondria, makes energy, but in cancer cells it's different. What happens in cancer cells?

Dr. Rutter: So cancer cells go through about half of that pathway. They take the carbohydrates about halfway through that pathway but they don't take the carbohydrate into the mitochondria, the powerhouse of the cell, they do other things with it, and specifically they use that carbohydrate to create the building blocks that will enable them to make a new cell. So obviously cancer is a disease of overgrowth of cells dividing and duplicating themselves more rapidly than they should and that's what creates a tumor, or what creates the cancer.

Interviewer: I think your work really argues that there's a protein called MPC1 that is a key component of this shift in metabolism. What is MPC1?

Dr. Rutter: The MPC1 and MPC2 together make up a protein complex that enables carbohydrates in the form of a specific molecule called pyruvate to enter the mitochondria, again the powerhouse of the cell, and enable the mitochondria to then take that pyruvate and use it to create energy.

Interviewer: And what happens to this protein in cancer cells?

Dr. Rutter: We've shown that in a large number of cancers, most prevalently in ovarian cancer, that the part of the genome that encodes this protein is just lost. It's lost from the genome and therefore the gene is not expressed, the protein isn't made, and this MPC protein complex is just never formed. So what we did next was pretty simple in that is the hypothesis is that it being lost is actually important then what if we put it back in and force the cancer cells to make this protein, and what happens is they lose their ability to behave like cancer cells. Their metabolism reverts from the way that most cancer cells do in metabolism to be a much more normal type of metabolism and they lose the ability to form tumors in different situations, and so...

Interviewer: Wow, that's amazing.

Dr. Rutter: Yeah.

Interviewer: So you saw that effect both in a dish but also in the context of an animal too, correct?

Dr. Rutter: That's right. So yeah exactly, we saw it in a dish and then the gold standard for this type of experiment is to put tumor cells, cancer cells, into a mouse and ask whether they can form tumors, and what we found is that the cells that had this protein, this MPC protein, put back in were quite dramatically impaired in their ability to form tumors in mice and how fast those tumors grew.

Interviewer: What kind of difference are we talking about? I mean is it there's a tumor compared to no tumor, or is it a difference in size, or is it the number of tumors that form, or...?

Dr. Rutter: Yeah that's a good question. I would say the way that the experiment was done it really wasn't done in such a way that we could see a tumor versus no tumor. So what was done is to inject about 100,000 cells into the flank of a mouse and then so that you already have a fairly large number of cells there and then look at the ability of those cells to grow, form a tumor and how big that tumor becomes, but always they grew slower when this MPC protein was put back in.

Interviewer: When you're talking about the progression of cancer where do you think metabolism fits in the scheme of things? Do you think it might be one of the early changes that must take place in order for a cell to become invasive for example or...?

Dr. Rutter: Yeah we do, we actually know that. In some cases that there are certainly many cancers where one of the early steps is to manipulate the metabolic profile of those cells.

Interviewer: And what are you most excited about going forward?

Dr. Rutter: Well I think there are a few different things that I would say we're most excited about. I would say first is just trying to understand what is the cause of the failure of the cancer phenomenon when we force cancer cells to make that protein. We just really don't understand it and whatever the answer is it will be interesting, and then the second, like we've talked about, is to try and understand how to exploit this observation to make a difference in the context of the treatment or diagnosis of cancer, and we have some ideas that I think are quite good as to how to try and translate that into direct clinical application.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

Interviewer: Alzheimer's 101. What is it? What's happening in the brain? What are some of the symptoms? What can be done, and what's on the horizon for potential cures. We're with Dr. Norman Foster, Director of the Center for Alzheimer Care, Imaging, and Research at the University of Utah.

First of all, let's talk about what is Alzheimer's? What are the characteristics of Alzheimer's, and what's actually happening in the brain? I find that kind of interesting.

Dr. Foster: Alzheimer's disease is a progressive disease of the brain that causes loss of nerve cells, and as a result patients first develop difficulty with memory. But then increasingly over time have difficulty with other areas of thinking and then eventually difficulty with daily activities so that they become dependent on others.

Interviewer: When you say nerve cells, is it brains cells?

Dr. Foster: These are brain cells. Yes, that's right.

Interviewer: These are brain cells. And what exactly is happening in the brain? I've heard it described as plaque of the brain. Is that accurate or not?

Dr. Foster: Well, Alzheimer's disease is caused by an abnormal accumulation of two proteins that normally occur in the brain, but in this disease abnormally aggregate into plaques and into tangles. And we now understand a lot of the basic biology of these uncontrolled protein accumulations. But we don't understand what sets this process off.

Interviewer: So these proteins start accumulating in the brain. Do they actually adhere to brain cells?

Dr. Foster: Not directly. They adhere to each other. So they begin with small fragments of protein, and then they aggregate into clumps. And then eventually form these plaques, or in the case of the tau protein, which makes the neurofibrillary tangle. These fibrils actually kind of have a spun or twisting appearance and interfere with normal nerve function.

Interviewer: It's kind of gumming up the works.

Dr. Foster: That's right. This is a disease that as far as we know just involves the brain.

Interviewer: So you spoke earlier about the symptoms. What are some things that if I'm a relative of somebody that I believe might be getting Alzheimer's I would want to be looking about for?

Dr. Foster: Well, the characteristic feature that late in life, on average in the mid-70s, people begin to have difficulty with memory. And, of course, we all have memory complaints.

Interviewer: Yeah.

Dr. Foster: And our memories are not perfect. We don't work like computers, but in these cases it interferes with a person's ability to do daily activities that they've been used to carrying out independently.

Interviewer: So, for example, perhaps they forget where they are when they're driving someplace where they've driven to numerous times.

Dr. Foster: That's possible. This is why medical attention, medical advice is so important because there's some things that are obvious, but we think it's very important to pick these up when things are not so obvious. And so there may need to be medical judgment.

One of the examples that I would use having trouble remembering exactly where I parked in a large shopping mall. That's normal, but after four or five hours not being able to figure out where it is or how to get help, that's abnormal.

Interviewer: Or how to get help. That's an interesting addition as well. When speaking of Alzheimer's, what can be done if you go and you talk to a physician to help you find some of those non-subtle things, your family member has been diagnosed with Alzheimer's, what then?

Dr. Foster: Well, I think the first important step is to know what is going on. It's quite a step. In fact, there's quite a bit of effort to evaluate what the cause of memory problems and cognitive problems are.

Interviewer: It could be something other than Alzheimer's.

Dr. Foster: It could be something other than Alzheimer's. It could be Alzheimer's with something else. For example, sleeping medications are common. Even over the counter sleeping medications can make Alzheimer's disease significantly worse, or it can cause symptoms that mimic Alzheimer's disease.

So first, making sure you know what you're dealing with is important. And then that, of course, will lead to what should be done about it.

Interviewer: Okay.

Dr. Foster: So there are many things that can be done about Alzheimer's disease where medications that are approved by the Food and Drug Administration that we know have benefits. Unfortunately, they're only modest right now, so we're looking for much more effective drug treatments.

Interviewer: Does that slow down the onset of Alzheimer's'? Does it get some memory back? What do these drugs do?

Dr. Foster: Well, the medications that have currently been approved by the F.D.A. compensate for chemical losses that occur in the brain typically in Alzheimer's disease. So many of them are very specific for Alzheimer's disease, and don't affect or improve all kinds of memory and thinking problems. But this is actually the kind of chemical byproducts of the plaques and tangles rather than getting at the plaques and tangles themselves.

Interviewer: What do those chemical byproducts do?

Dr. Foster: Our nerve brain cells talk to each other by what are called synapses. So there's a chemical that's released at the end of one nerve that is then picked up by another nerve. And so when nerves are sick, they have difficulty synthesizing, creating this chemical message system, and that's what these drugs do is try to compensate for that, restore some of the chemical changes that are lost in Alzheimer's.

Interviewer: What else can be done? So you've got some medications. What are some other options?

Dr. Foster: Right. So right now one of the important things to do is help the patient. The patient needs to have help with day-to-day activities or doing things. For, example, if it's only memory problems, then one of the things you need to do is write down things so that you can read and to see what you remember.

We can no longer do or depend upon some things that we took for granted before. So, for example, you're in the doctor's office. The doctor says, "Come back and see me in two weeks," and they give you a date. And then after the doctor leaves the office if they haven't written it down, you don't remember that day.

Interviewer: Yeah.

Dr. Foster: Now, maybe that could happen with any of us, and it's always a good idea to write those down or keep a calendar. But if you know that you have Alzheimer's disease or a memory problem, that's something that you really have to pay a lot of attention to. But there are other things that are very predictable. Complications, I call them, of Alzheimer's disease that need to be addressed.
Other Effects of Alzheimer's

For example, people who have memory problems get embarrassed by this, and so we often see that patients and often other family members become socially isolated. That's exactly opposite of what people with this disease need. They need to be interacting with others, have a good quality of life. And not leaving your house, and sometimes the wife or husband not leaving the house also, that's bad.

Another example is social activities. You may be embarrassed because of memory problems and withdraw from your friends at the very time that there's most important to you. And then also there can be problems with family. A family doesn't understand what's going on. They misunderstand and, therefore, act on assumptions that they make that are in error, particularly if they haven't sought medical advice to understand what's going on.

So one daughter might think, "Well, he's just trying to get back at me. That's why he's not doing things." Or "I think he's just depressed so we should try to make him happy." Or that this is related to medication. There are all sorts of possible explanations, but the family members are pulled apart by disagreements and conflicts, not being on the same page about how to support their loved one. Then we often see disasters, complications not just socially but within families because of this disease.

Interviewer: It appears as though the Alzheimer's affects the brain. Does it otherwise affect you physically directly, or is it the indirect effects? You're embarrassed. You don't leave the house. So now you're not getting any exercise. You're not getting any social interaction. Is that where a lot more of the danger is?

Dr. Foster: Well, I often get asked questions about whether Alzheimer's disease kills? And we know the people who have Alzheimer's disease at every point in their illness are at greater risk of death. Now, this doesn't just happen because of the plaques and tangles, but because we depend on our brain for many things.

Interviewer: Yeah.

Dr. Foster: You just described some of them. Our motivation, for example, get up and go, all of that sort of thing makes a big difference in our physical health. We know that people should be active, but also it affects our ability to seek help. For example, if you have chest pain and you're not able to seek help, then you're going to die from a heart attack more likely than somebody who does seek help.

If you forget the medication that you need to take for diabetes, then you're going to have complications of diabetes and die from that earlier. Our brain also-in ways that we don't as much understand-are involved with basic daily function and maintaining our physical health. So that people who have brain injuries, whether it's due to trauma or other things die earlier than people who have good functioning brains.

Interviewer: Let's talk about some potential cures or things on the horizon that excite you. I know that you keep very in touch with the research that's going on in the United States and the world. Is there hope on the horizon?

Dr. Foster: There is hope. We know much more about Alzheimer's disease. And I think one of the important things to recognize is that Alzheimer's isn't simple. It's a complicated disease. There are two proteins that accumulate. They affect the brain in complex ways. They change the chemistry of the brain.

So I think that it's unrealistic to expect that we're going to find a single drug or penicillin that's going to cure the disease. It's much more similar to cancer. We're going to make gradual, progressive improvements step-by-step, identifying how this disease develops and stopping it in its tracks.

And, of course, a lot of our efforts now are in trying to develop treatments that we would give early in the disease before there's so much damage to the brain. So we think that it's much more difficult after there is so much damage to the brain of correcting the problem. So early identification, early treatment is the way we're going, and there are many exciting possibilities.

We know that these two proteins that accumulate in the brain do so when they get slightly off balance earlier in life. So these slight differences or the slight imbalance over a period of years becomes devastating to the brain. And if we can offset even in a little way this imbalance, then we'll be a long way to brain health.

In addition, we know that the brain is not static. The brain can change. The brain, we call this plastic. It responds to differences in the environment, and there's good evidence now that some older individuals have resistant brains to these effect. And the resiliency is one of the things that we're trying to capitalize on, understand why some patients are so devastated by the same changes that can have less effect in others.

It's time for us to give the best care to patients with Alzheimer's disease. They deserve the dignity and dignity of care.

updated: December 2, 2020
originally published: September 25, 2013