UC San Diego Researchers Answer Key Alzheimer's Question
August 12, 2013 2:09 p.m.
Subhojit Roy, Associate Professor Pathology & Neurosciences, UC San Diego
Dr. Maria Carrillo, Vice President, Medical and Scientific Relations for the National Alzheimer's Association
Related Story: UC San Diego Researchers Answer Key Alzheimer's Question
MAUREEN CAVANAUGH: Coming up, UC San Diego researchers try to unlock the secrets of how Alzheimer's disease begins in the brain. It is 12:24. You are listening to KPBS Midday Edition. This is KPBS Midday Edition. I am Maureen Cavanaugh. Researchers into Alzheimer's disease have puzzled for some time about why previously healthy brains develop the disease. As it turns out we all have the same ingredients in our brains that can lead to the development of Alzheimer's so why don't we all get it? A research team at UC San Diego school of medicine asked that question and their study produced some intriguing results. Their work was published just last week in the medical journal Neuron. I'd like to welcome my guests. Dr. Subhojit Roy is principal investigator of the paper and associate professor of pathology and neurosciences at UC San Diego and Dr. Roy, welcome to the program.
SUBHOJIT ROY: Thanks for having me.
MAUREEN CAVANAUGH: Maria Carillo serves as vice president of medical and scientific relations for the national Alzheimer's Association and Maria welcome so much to the show.
MARIA CARILLO: Thank you.
MAUREEN CAVANAUGH: Now Dr. Roy, first of all tell us the basics out of the brains of people who have Alzheimer's differ from healthy brains? They exhibit some sort of plaque, don't they?
SUBHOJIT ROY: Yes so major pathology and Alzheimer's disease the presence of this amyloid plaque which is a structure that is not found in normal brains and what you see is that the whole brain is started with the sort of deposits of clumps of protein or globs if you will which are thought to initiate the disease and that is different in Alzheimer's brain from the normal brain.
MAUREEN CAVANAUGH: And how does that affect the function of the brain?
SUBHOJIT ROY: So it has been shown that the amyloid plaque are what actually makes the plaques which are not as amyloid oligomers have a dramatic effect and cause defect in brain and learning in a variety of different organisms.
MAUREEN CAVANAUGH: It's not as if something gets into the brain that causes these plaques they are actually made up of ingredients that are in everyone's brain is that right?
SUBHOJIT ROY: Exactly. So the amyloid plaque is made up of a protein known as the amyloid precursor protein because it's a precursor for the amyloid plaque and what happens is that the play precursor protein is chopped up into smaller segments and one of the segments actually makes his amyloid plaque. And that has been known for a very long time.
MAUREEN CAVANAUGH: So everyone, this is the question that you ask, if everyone has the substance inside their brain to create the plaques, why doesn't everyone develop Alzheimer's disease?
SUBHOJIT ROY: Exactly, so we all have large quantities of the insulin precursor protein that leads to the light plug and we also have large amounts of the enzyme known as base which is responsible for actually cutting board chopping up this amyloid precursor protein so we all have those. So the question is that if we all have those in our brains and if the amyloid precursor protein was being chopped about the time we would all have Alzheimer's disease. What we found interestingly was that as soon as the amyloid precursor protein and the base which is the chopper are made they are actually shipped into different transport organelles, and you can think of them as just shipping in two different people who are putting into different cars let's say into blue cars. So even though they are going on the same highway which is underway than Iran and the so the red and blue cars are different compartments, so they don't really need. So we think this is what is the natural track of your neurons by which they keep the co-conspirators at bay so that you don't get the disease.
MAUREEN CAVANAUGH: So as long as you keep the APP the precursor and the base separate, and Alzheimer's?
SUBHOJIT ROY: Absolutely, this has been shown quite a long time ago that if you remove the base the EPP cannot be cleaved. You cannot get the amyloid plaque without the base in it. So I think what we have shown is that it was not known that they travel in different compartments, so that is kind of
MAUREEN CAVANAUGH: What makes a neuron travel different compartments, what makes these two elements converge?
SUBHOJIT ROY: Okay so there are two questions there. What makes them travel in different compartments, that is because whenever the neuron makes different things, it just has a way of shipping different proteins in different compartments so that's what the neuron does a lot of different proteins behave that way and it just so happens I think probably due to evolutionary significance that a PP and these are packaged into different kinds of cars, but why do they converge in Alzheimer's disease is the second question and I don't think we really understand exactly why they converge in Alzheimer's disease, but what we found is that if you simulate conditions that are known to cause the convergence of these two, then you do get more amyloid beta, so in other words it has been known for a while that just and activation of neurons can lead to more amyloid beta, so if you activate (inaudible) neurons we found the convergence of the precursor protein and the base was also enhanced. But why does it exactly happened in patients with Alzheimer's disease? We don't know yet except we do know that it does happen because if you look at brains of people who have APP and base that looks separate but they are converged in Alzheimer's disease.
MAUREEN CAVANAUGH: So Dr. Roy, what you are saying is that in laboratory show that activating neurons justly to this convergence, but we don't know what causes and activation of neurons in someone's brain that might lead to a convergence which would lead to Alzheimer's?
SUBHOJIT ROY: Are we don't really understand what the relationship of brain activation is to Alzheimer's disease.
MAUREEN CAVANAUGH: Okay, it just happens in the lab.
SUBHOJIT ROY: Right.
MAUREEN CAVANAUGH: Okay, let me go to you Maria and most people will not develop Alzheimer's in their lives but the number of people who do is expected to increase dramatically in the next decades is that right?
MARIA CARILLO: It's right and it certainly unfortunate that we are starting to see the Alzheimer's epidemic here with the baby boomers starting to turn 65 but unfortunately we have 45 million Americans living with Alzheimer's disease today and the number is set to triple by 2050. Unfortunately with that of course is all of the costs associated with it with today are over $200 billion and can increase to almost 1,000,000,000,000 by midcentury and of course the human costs of the burden of the disease. I have someone come a loved one in my family with the disease and certainly understand firsthand what that looks like trying to care for our loved one at home.
MAUREEN CAVANAUGH: And it sounds like more people are going to experience this firsthand as we go toward as you say this epidemic of Alzheimer's. What is your reaction. To research like this we are learning so much more about the disease?
MARIA CARILLO: I think it's an incredibly exciting time as a neuroscientist myself by training and working with all of these compounds, it's been a fascinating transition for me to be able to see from the thunder's point of view, Dr. Roy has been funded by the all swimmers Association is the lintel of the strategic approaches towards trying to stop Alzheimer's disease in its tracks have to be pursued no stone can be left unturned as they attempt to look for a way to either delay or completely stop Alzheimer's disease progression. And so we are really excited by the variety of approaches of Dr. Roy's included as well as many others that are looking at different avenues to treat Alzheimer's disease.
MAUREEN CAVANAUGH: I'm wondering, Dr. Roy, what you believe is the significance of this research? Of your research?
SUBHOJIT ROY: I think what is one of the most exciting aspects that I find is that if you can actually keep these two proteins APP and base at bay than potentially you would be able to able to prevent the plaque deposition and Alzheimer's disease we are talking about the physical interaction of two proteins and you know there are a lot of compounds which are used for example in cancer therapy that actually prevent protein protein interaction, so that to me is an interesting avenue that I don't think people have really looked at the actual physical interaction between base and how that might lead to a potential therapeutic (inaudible).
MAUREEN CAVANAUGH: As you think about this, as you surmise what might, of this information, would you be thinking of introducing a compound perhaps by injection, by a pill, where do you see I mean, introducing an element that would keep these two things APP and base separate?
SUBHOJIT ROY: So that is a great question and I think one of the reasons why therapeutic interventions in the brain have kind of lagged behind for example cancer research is because it is just really hard to get things into the brain and as you know that's actually in terms of evolution, that's very advantageous, to human beings, that you can't have everything going to the brain but the same time it poses a tremendous challenge to researchers to do that. But at the same time there are many compounds that are in clinical trials right now that can reduce the amyloid beta peptide and they are probably you know more about it than I do but they are in clinical trials right now and we will have results in a year or two.
MAUREEN CAVANAUGH: Maria Carillo, is this an interesting and exciting time when you said perhaps thinking about new drug therapies for the treatment of Alzheimer's or to prevent Alzheimer's disease?
MARIA CARILLO: Absolutely. I think that the way that we look at amyloid in the brain, there is a plethora of ideas is just surrounding amyloid but I think that exciting idea about this is we are also looking at (inaudible), the nerve tangles actually play a role and how inflammation plays a role, how cell energetic scleral mitochondria, the little gas pumps in your brain that actually give you the energy, all of these aspects how does insulin resistance and diabetes play a role, how does vascular dementia and vascular incidences potentially play a role how does maybe epilepsy and having an epileptic attack or maybe a stroke may be also increase your propensity for Alzheimer's. So it's all complicated system all interconnected and really interdependent. So it is a little simplistic to think that one change along actually makes a difference and I think what the field in general is looking at is trying to find a variety of therapeutic approaches so that we can really learn from the AIDS field in terms of the cocktail approach. How can we actually intervene with Alzheimer's disease at various stages and various proteins that we now know play a role in this disease.
MAUREEN CAVANAUGH: And what about the treatments perhaps the drug therapies that are available right now, how effective are they?
MARIA CARILLO: So certainly we have some symptomatic treatments available and they are FDA approved. You know, their effectiveness varies from individual to individual. Certainly some individuals have even a difficult time with the G.I. effects right just having stomach problems or other side effects were they cannot take the pills but now the advent of patches has helped circumvent that and we think that there's two to six months to maybe two years or more in different people there are reports that there are effective for certain amount of time. They are really only helping with the symptoms so they help you maintain your cognition for a little while but the disease can unfortunately continues to unfold in the body and brain and ultimately will overpower what happens with those symptomatic treatments. So we are definitely looking for new treatments. We have to have a way to trench the trajectory of this disease in San Diego alone in San Diego County it is the third largest cause of death in people in San Diego over 65.
MAUREEN CAVANAUGH: Which is why basic research like Dr. Roy's is so important. I have to end it there. I've been speaking with Maria Carillo. She's vice president of medical and scientific relations for the national Alzheimer's Association and Dr. Roy is associate professor of pathology and neurosciences at UC San Diego thank you both very much.
SUBHOJIT ROY: Thank you.
MARIA CARILLO: Thank you.