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Control Brain Disorders with a Switch

Control Brain Disorders with a Switch

Daniel Zwilling, PhD discusses unimaginable opportunities that could become reality in helping to cure psychiatric disorders and nuerodegenerative disease including Alzheimer’s and Parkinson’s disease.


Frank:  I'm extremely excited about our guest, I'm excited about all of our guests, but we have with us Dr. Andrews-Zwilling.  She's originally from Trinidad, Tobaggo, which is by the way, I've been there, it's beautiful there, where she completed her Bachelor's of Science & Biochemistry, and Chemistry.  From there she went to train at the prestigious Max Planck Institute, I don't know if I pronounced it right, for experimental medicine in Germany where she received both her Master of Science and PhD in Neuroscience. Today Dr. Andrews-Zwilling is establishing her own research program to develop drugs that block the detrimental effects of, it's called apoE4 which we're going to learn what that is in a moment on nerve cells and in collaboration with Dr. Mahley at the Gladstone Institute. Dr. Andrews-Zwilling is the recipient of many awards including the Award for Young Scientists from the Alzheimer's Association and the National Award for Excellence in Science from the National Institute of Higher Education Research Science & Technology, the Ministry of Science & Technology in the Caribbean Academy of Science.  Dr. Andrews-Zwelling it's just a pleasure to have you on the Aging Boomers.

Dr. Andrews-Zwilling:   Thank you so much for asking me to be on.  Thank you.

Frank:   I could've gone on with a lot of accolades about your background, but I don't know if we would have time for the interview.

Dr. Andrews-Zwilling:   [Laugh].  Thank you, that was a very generous introduction, thank you. I appreciate this.

Frank:   Well, you deserve it. So, why don't you tell us a little bit about Gladstone Institute, kind of what happens there, your role.  Tell us a little bit about that.

Dr. Andrews-Zwilling:   Ok thank you.  So the Gladstone Institute is an Independent Biomedical Research Institute, and we are based on the Mission Bay Campus in San Francisco.  We are affiliated with UCSF, so we have a very strong collaboration with them, but we are an independent research organization.  And we tackle some of the major diseases affecting mankind today. So we have three institutes within the Gladstone.  The first is the Institute of Immunology & Virology.  On there we research HIV, diabetes, hepatitis, and some epsilon.  Then we have the Institute of Cardiovascular Disease, where we look at heart disease and also stem cell technology which is a really big field right now.  And then finally the institute that I'm a part of is the Institute of Neurological Disease. And within our institute we look at Alzheimer's disease, Parkinson's, Multiple Sclerosis, and so on.  So we tackle all of the major diseases affecting mankind today.

Frank:   You got your work cut out for you.

Dr. Andrews-Zwilling:   Yes, definitely especially with the neurological diseases.  It's a very difficult area to work in, because the mind is so complex, so yes we do have our work cut out for us.

Frank:   Tell me, tell our audience, you know, is it even possible to determine how many people have dementia today?  If so, do you know approximately what those numbers are, and what do we see changing over the next couple of decades?

Dr. Andews-Zwilling:     So, that's a really good question.  Let me start by first defining what some of these terms are.  Dementia is just a general term for decline in mental ability severe enough to interfere with your daily life.  Memory loss is one example of this.  Then Alzheimer's disease is the most common type of dementia.  And when we are talking numbers, according to the Alzheimer's Association, currently we have 5.1 million people living with Alzheimer's Disease.  This number is expected to triple by mid-century and this doesn't even include other forms of dementia. Alzheimer's disease is just one form.  Then if nothing is done to change the course of this disease, by 2050 the estimated cost associated with caring for and treating Alzheimer's disease patients could be as high as one trillion dollars in the U.S. alone.  This does not even account for the intangible cost of diminished quality of life, both for the patient and for their caregivers.

Frank:   Do you think we're prepared?   When I say we, do you think the United States is prepared for what's going to happen?

Dr. Andrews-Zwilling:   Uhm, I don't think so.  I mean, I think there is definitely a lot more awareness right now because of people like you and all of the boomers who no longer accepting that dementia and Alzheimer's disease is a normal part of aging.  This is what has to happen.  So, it's definitely more money going into research and trying to figure out what causes Alzheimer's disease, how can we prevent it, how can we cure it.  But, I think the shared number of people that are currently living with Alzheimer's and as I said is going to triple and then go on and on as we all age, I don't think we are fully prepared for what is coming which is why cases like the Gladstone and people who do try to figure out the role of basic science and investigators like me, it's really critical to find solutions to these complex diseases.  That's really the only way we're going to try to change the outcome.

Frank:   I know you mentioned earlier Alzheimer's is a form of dementia. You don't have to get into the detail, we don't have the time for it on the show.  But, why don't you briefly go over the types of dementia that we're dealing with.  Then, just very briefly, maybe the differences between those types of dementia and Alzheimer's.

Dr. Andrews-Zwilling:   So, basically, depending on what part of your brain you have neuronal or nerve loss, this then leads to the type of symptoms that you see.  For example, as I said,  dementia is just a general term for decline in mental ability but severe enough to interfere with your daily life.  With Alzheimer's disease, it starts off with memory and then it progresses.  With other types of dementia, for example, vascular dementia or frontal-temporal dementia or even dementia associated with Parkinson's disease, these all lead to a decline in your mental ability  but depending on the part of the brain that is affected, that determines then the type of difficulty that you have. One really common form of neurological disease that people know in addition to Alzheimer's is Parkinson's for example.  And in Parkinson's disease the cells that die are within the center of your brain that is responsible for motion and movement.  So with Parkinson's for example you have the tremor, the rigidity, and the inability to initiate movement and that's because that particular part of your brain is breaking down.  In Alzheimer's it's because the hippocampus, which is the part of your brain responsible for your memories, this is the part of the brain that's breaking down.  And that then leads to the symptoms that we see.  So, depending on the place that you have the brain loss, it then leads a loss of that particular function in your daily life.

Frank:   So when somebody says and I hear this all the time, "I think my dad's fine.  He doesn't remember things that just happened, but boy, he could get into a lot of detail of what happened many years ago."  How do you respond to that?

Dr. Andrews-Zwilling:   Uhm, this is kind of in the early stages for example of what could be Alzheimer's disease.  This is because as I said the area of the brain called the hippocampus, this is the area that's responsible for forming new memories.  So that's why in the early stages of Alzheimer's disease  it's often things that just happened recently, where you parked your car, where you put your keys.  We all have lapses in memory especially today when we're multitasking while on the phone, etc.  It's only because of the problem when this loss of memory is really affecting your daily life.  You can't remember where you parked your car, and this has been a problem, you don't remember that you left the stove on, for example. So, in the early stages, yes, you forget recent events, but the long term memories, those are not stored in the hippocampus which is part of the brain that initially breaks down.  Those are stored somewhere else in your brain.  So that's why early on in Alzheimer's you lose the more recent memories because you can't form those and hold on to those.  But the long term memories that you have from childhood and early marriage, those are intact initially.  But as the disease progresses, the patient also lose those memories.

Frank:   Yeah, I can't remember who told me this, but I use this example quite a bit.  You don't have dementia or anything. Don't worry if you misplaced your car keys.  The worry would be if you didn't know that the keys were for a car or if you even have a car.

Dr. Andrews-Zwilling:   Exactly, exactly.

Frank:  Ok great!  I know there's people listening who may have had a loved one in their family who has had Alzheimer's or another form of dementia and they worry.  Am I going to get it now because my mom had it?   What research has been done as far as whether or not it is heredity or not?

Dr. Andrews-Zwilling:   That is really an excellent question. There's definitely a small portion of the population of Alzheimer's disease patients where it is a hereditary factor.  This is about 5 to 10% of all cases. In this case, it's a mutation in particular genes that have been identified.  One of the gene is called ameloid precursor of gene, APP.  Mutations of these genes are the processing of this protein leads to early onset Alzheimer's disease and this is where patients get the disease in their 40's or 50's.  This is relatively rare.  The vast majority of cases are the late onset and sporadic form of Alzheimer's disease. There are different cause that can lead to this.  One of them, the major risk factors that lead to getting Alzheimer's disease at all is aging. So, the older we get the more likely once you cross 75, 85, etc, there is then a risk that you do develop Alzheimer's disease because is the biggest risk factor.  Then within this late onset population, there's also another gene called apoE, and apoE4 which is the protein that I work on.  This also contributes significantly.  It's a major risk factor for developing Alzheimer's disease.

Frank:   So is there a way to determine if someone has apoE4?

Dr. Andrews-Zwilling:   Yes there is.  One can do a genetic test.  This is one of the readouts that you would get.  If you are apoE4+ or not.  One thing I should mention is that we all have apoE4 protein.  There are two major forms of the protein, apoE3 which is the more common form about 75% of the population has it, then apoE4 which is the form that predisposes you to getting Alzheimer's disease.  So, one in four of us, for example, is an apoE4 carrier.  If you do have this apoE4 protein, it increases your risk of getting Alzheimer's disease and it also  decreases the age of onset of getting the disease.  You can get tested to find out if you are an apoE4 carrier.

Frank:   So if you're an apoE4 carrier, it doesn't mean that you're going to get the disease.

Dr. Andrews-Zwilling:   No, your risk of getting it is simply higher,  than if you're apoE3 carrier.  One thing I'd also like to say, apoE3 carriers can also get Alzheimer's disease.  Your risk is lower, but as I said, once you cross a particular age, then it's still a risk, that even if you are an apoE3 carrier that you can get it.  Your risk is simply higher, significantly higher of you're an apoE4 carrier.

Frank:   So, why would I want to know if I was an apoE4 carrier.  Why would I even want to know?

Dr. Andrews-Zwilling:   I think it depends may on your personality and how you view having this knowledge, because currently, we don't have effective drugs to cure or slow down or treat Alzheimer's disease.  If you did have the knowledge that you are an apoE carrier and know when you have a higher risk of getting the disease, there's nothing specifically you can do with respect to taking drugs to help, but there's definitely lifestyle changes that you can have which you should have anyway, but if you know that you're a carrier and if this knowledge would prepare you for example to do more things that would try to stave off Alzheimer's disease later in life, knowing that you have a higher risk, then this is definitely something that you should do.

Frank:   So give us an example of some of these lifestyle changes, what could people do?

Dr. Andrews-Zwilling:   There are a couple of things that you can do.  One of the main things that you can do is avoiding head trauma.  There is a huge risk that if one has some form of  brain injury, whether it is from playing contact sports or especially boxing for example, if you were to join the armed forces, and so on.  Avoiding any kind of situation where you can have head trauma would be the major thing that you can do.  Secondly, what's important for your heart is very good for your head.  So avoiding cardiovascular disease, exercising, avoiding diabetes and high blood pressure, and so on.  All of these lifestyle kind of changes that one can have living a healthy a life as much as possible is very, very important. And then thirdly, kind of the "use it or lose it" model, it's called cognitive reserve.  So the bigger cognitive reserve one has, it's kind of seen as a way that if you lose some later you had a bigger pool to lose from, so you're a little bit more protected. So, trying to be a life-long learner, learning new things, learning to dance which will also give you the exercise obviously, but trying to keep your brain as active as possible for as long as possible is also one major thing that we can do.

Frank:   Let me ask you a question, I think I know the answer to, but I think would be interesting to our listeners.  So, let's say I do crossword puzzles. I do it all the time and I pick up the New York Times, and now I just got it down and say, "Well, I'm keeping my brain active cause I do these crossword puzzles, but I'm an expert at it."  What would you say to that?

Dr. Andrews-Zwelling:  I would say that's excellent that you are doing these crossword puzzles, but at this point where you think you're an expert, maybe you should find something else that's also challenging you.  I think you should definitely continue with that because those puzzles are quite difficult, I'm not great at them myself, so maintaining it is definitely a great way to go.  But you should then try to challenge yourself with something else, some other mind-challenging project that you can think of.  And when you're done doing your crossword puzzle, you should go for a walk or a run.

Frank:   So, do something may be out of your comfort zone.

Dr. Andrews-Zwilling:   Exactly, something that should keep the mind going and also keep the body going.

Frank:   I tried, somebody told me, try brushing your teeth with your non-dominant hand.  Alright, so I tried doing it with my left hand, I just get toothpaste all over my face.

Dr. Andrews-Zwilling: [Laugh] That's a good exercise, yeah.

Frank:   So, this resesarch that you're doing is so important.  How do you feel the research for one day help with Alzheimer's disease or other forms of dementia?

Dr. Andrews-Zwilling:   There's lots of research going on in many different areas.  There are three major contributors, I would say, to Alzheimer's disease and these are based on three different proteins.  One of the major ones is the amyloid precursor protein, which is the protein that forms plaques in the brain.  There's a lot of research surrounding that area.  The second protein is called the tau protein and these form the tangles which form within the neuron and kind of kill the self from the inside.  There's a lot of research going on in that area. My area focuses on the protein that I mentioned before, apoE4, and how that causes pathology.  So, we have investigators here at the Gladstone that are working on all three of these areas.  In the case of apoE4, it causes its problems because the protein that's usually there to help protect your brain if there is some injury.  This injury could be a stroke, it could be a physical injury, or it could be aging because that in itself tends to damage the brain. The apoE protein is usually there for good to help protect your brain, but if you have the apoE4 which is the one that increases your risk of getting Alzheimer's, this protein can't do that job that it was meant to do and it recognizes it as having an abnormal shape trying to get rid of it and this causes a whole other set of problems.  So, the research that we're doing is trying to find a way to make apoE4 do the job it was meant to do by fixing the structure of the protein.  So what we hope is that one day the drug we are developing here at the Gladstone, that we would be able to use this to hopefully prevent the disesase from happening.  That would be our goal.

Frank:   I'm going to put you on the spot here.  I mean, you probably have a better feel for it.  Is it just one day, all of a sudden there's going to be an announcement saying, "We found the cure."  Or is it just known amongst you and your peers that this is going to take many, many years?  Which is it?

Dr. Andrews-Zwelling:  So, the optimist in me would like to believe that we would have an announcement, that we would have a cure.  The realist and the scientist knowing the daunting past that we have ahead of us especially because of what they said they are.  Alzheimer's disease and the pathology and the clinical symptoms that one had is kind of the end result.  But we know that there are many roads that lead to what this end pathology and clinical problem that the patient has. So, I think there would have to be maybe some sort of combination of therapies one day that will be used because you have the amyloid building up.  You have the tau proteins form in the tangles in your neurons.  You have the apoE4.  So you have all of these different angles that are leading to the problems and these problems actually began decades before you have the clinical symptoms.  So I believe we would hopefully one day have would be something that we can take that can help to prevent this disease from happening. I don't think that once you have the disease that we would have the cure, because as I said what you're losing are the brain cells that hold your memory.  So there's no drugs that could bring those brain cells back and bring back the information that they stored.  But what we can hopefully do is prevent the loss of these brain cells by treating relatively early in the progression of the disease.

Frank:   That's a very good point.  Well, it's positive, it's just hard for someone who has a loved one with it, knowing that there's no way of turning it back but that's just, you know, the reality.  As you know I am a consultant in the business.  I'm just seeing more and more younger people and I'm talking even into their 40's and 50's and early 60's being diagnosed with dementia, with Alzheimer’s.  Is it that I'm just seeing that or you hear, is statistic showing that more and more younger people are getting it or just more aware?

Dr. Andrews-Zwilling:   I think we are more aware.  The people who get very early onset of Alzheimer's disease, that's a relatively small proportion of the population.  But I think because you are as you said in the business, and you are very aware of the symptoms and you're dealing with this kind of on a daily basis, I don't think the numbers necessarily of the people who are getting it younger are increasing.  That's a pretty defined set from this hereditary form.  But the shared number of people who are living past a certain age is definitely increasing.  So that then increases the population. As I said right now we have 5.1 million people and this is just in the U.S.  This is number is going to triple.  So that just tells you, as a population ages and we have a larger and larger pool going into this risk group, this is why we're seeing more and more numbers of  people having the disease.

Frank:   Do you happen to know that 5.1 million that you bring up, is that what we're aware of or is that what we're aware of plus figuring a certain amount more that have it that we're not aware of?

Dr. Andrews-Zwilling:   That is actually an excellent question.  I think that might be the numbers that we are aware of because obviously there would be some patients who are taken care of by their family members at home and who are not necessarily brought into the clinic and the family decides that they can't handle the situation and deal with it at home, so they definitely might be a proportion of patients who are not seen by clinicians and who are not clinically diagnosed with Alzheimer's disease.  This is very possible.

Frank:   Yes, so those numbers could be quite a bit higher.

Dr. Andrews-Zwilling:   Yes, they can definitely be a bit higher.

Frank:   So, we have a couple of minutes left. I'd love for you to talk about the Gladstone Institute a little more if people wanted to get more information in what you're doing and your peers are doing.  Could they go, is there a website that they could go to?  What do you recommend as far as people want keeping up on your research?

Dr. Andrews-Zwilling:   Ok, that's a great question.  Thanks for asking.  You can go to www.gladstoneinstitute.org and there we have a really fabulous webpage that you can get an overview of all the different forms of science that we are doing here at the Gladstone.  The work on Alzheimer's disease is major but it's just one area that we are researching.  As I said we do work of immunology, virology, stem-cell research which is really huge right now at the Gladstone, cardiovascular disease, and then different forms of neurological disease.  So you can check out www.gladstoneinstitute.org to find out more about us.

Frank:   I just want to thank you for all you do.

Dr. Andrew-Zwilling:     Thank you very much.

Frank:   It's tremendous.  It is such as need.  I hope, let me ask you this?  If somebody wanted to even contribute to this from a dollar standpoint, does Gladstone take contributions as well to help in this research, or is it coming through the Alzheimer's Association?  How does that work?

Dr. Andrews-Zwilling:   Definitely.  We do receive funding from the federal government, from funding agencies like the Alzheimer's Association, and you can imagine the number of federal dollars has decreased a little bit over the years and there's a lot of competition for funding.  The need for money to support our research is definitely critical.  So, there is a link on our website called Supporting  Gladstone that people can go to if they want to donate to one particular area or simply to the Gladstone itself to support our research because this is another area we have gone to support the research is looking at private funders.  So this is definitely possible.

Frank:   Dr. Andrews-Zwilling it was a pleasure to have you on.  We got to have you on again because I know there's going to be more and more developments going on with this research.  I hope you'll join us again in the future.

Dr. Andrews-Zwilling:   Thank you so much.  Thank you for having me on, and I also wanted to thank you for the work that you are doing, to raise awareness about the disease and about research that's going into it.  It's really critical to have voices like yours ago.  So, thank you.

Frank:   You're very welcome.  Thanks for joining us on the Aging Boomers.  What you all can do to help is go to itunes and download not only this podcast but all of ours.  You could go on registering for it and share it with others so we help educate people out there on all these issues facing boomers, their parents, and of course an aging population.  You could also go to my website at the agingboomers.com to see the podcast as well.  And again, thank you for joining us.  Have a safe week and we'll talk to you all soon.

Control Brain Disorders with a Switch