Big Think Interview With Ottavio Arancio

A conversation with the professor at the Taub Institute for Research in Alzheimer's Disease and the Aging Brain at Columbia University.
  • Transcript

TRANSCRIPT

Question: Can you describe your research into Alzheimer’s disease? 

Ottavio Arancio:  Okay, the overall goal of the research in my lab is to find a therapy against the Alzheimer’s disease.  That’s a very general way of saying things and to be more specific we are… we have different strategies in the lab to go to achieve this goal, so we are trying to approach it from different perspectives and if I have to summarize these perspectives in a few words I should say that in one kind of studies we are trying to understand what is the function of a molecule that is called beta amyloid and this is a molecule made by many amino acids.  Once there are many amino acids together those molecules are called peptides.  Anyway, this beta amyloid, which is produced in a very high amount in the brain of people with this disease and is known also to be very toxic to the communication of the cells in the brain and therefore to lead to memory impairment, so but we know that this molecule is present in the brain of people throughout life, just normal half the people and it is there in very low amount and nobody knew what was the function, if at all to any function this protein in this very low amount.  What most of scientists thought was that it was kind of piece of garbage in the brain of people with no relevance whatsoever and instead we have started working on it and we have found that actually probably the very likely function of this protein in very low amount is just to be there to lead to normal memory, so without it we cannot store information in the brain, we cannot learn and there will not be normal memory. 

So I mean with all the study what we think is that this molecule is there.  It’s necessary for memory and then for some unknown reason we start making…  people with the disease start making a lot of it and the fact there is a lot just makes opposite of what it does in the normal brain, so it’s actually it reduces memory when it is there in a very high amount and so this is a very, very you know interesting characteristic and we think that actually until the studies were not there what people were doing to understand the cause of the disease was just to look at the disease from the very end of it instead of trying to understand…  You know it was a kind of a piece of a puzzle that is missing to understand the… to understand how something which is there becomes what is the beginning of the end for memory.  So in other words just to make things more simple because otherwise we get lost here is that now we know that normal function of this protein in very low amount in the brain is to lead to memories, that this molecule is necessary for memory and that we now need to understand how the problem starts, how memory is impaired.  We need to understand how this normal regulation of the level of this protein in the brain is broken and so the brain starts to make a lot of it.  So we think that through this study and through establishing what is normal function of the protein we could understand at the very beginning of the disease and once you usually understand how this starts, which is something which we really do not have it so far.

Question: Can you explain how this protein contributes to memory loss?

Ottavio Arancio: What I found is that the normal function of this protein is there to lead to memory, the opposite of memory loss.  So now I would like to understand the bridge between the normal function of this protein, which is just to lead to memory to its abnormal function, which is the memory loss.  You see, so the fact that the protein gives to memory loss is something that was already known by scientists.  It’s slightly different.  I don’t want to take credit of something I did not discover.  What I have discovered is that this protein in normal low concentration leads to memory.  It leads to memory loss the opposite only when it is there in very high amount, and I would like to bridge the gap between its normal function and its pathological function, its bad function.  How does a good turn into a bad guy?  How does a good protein turn into a bad protein?

Question: What factors affect our memory?

Ottavio Arancio:  One of the biggest factors that can affect it is attention for instance.  I mean if you do not pay attention to something it’s very likely that you will learn what you have… yeah, what you just saw.  For instance, just to make an example I bet that many people… many of us remember what we did on September 11 because you know there was a coincidence of just we paid particular attention to all what happened that day.  I bet that much less people will remember what happened the day before or 2 days before.  So that’s… attention is also… is very, very important.  Another factor that is very important would be motivation to…  If you don’t care about doing something you will not learn about it if you are depressed or things like that, you will not learn what you just saw, what you just did.  You will not memorize what you just did.  Obviously you need to be able to perceive the stimulus.  If you cannot see, no way that you will remember or if you do not hear you cannot remember words.  So we need to be able to get to those things.  This is stuff that we…help remembering.  Obviously those are not the only things because we can monitor also through chemicals and other ways also memories and hopefully in the future we’ll be even better at that.  So we can also stimulate memory chemically. 

Question: How do memory enhancing chemicals work?

Ottavio Arancio:  What they do, they will work at the level of the synaptic connection and since at the time of memory there is a chain of chemical reaction at the level of the synapse, but chemical means the same…protein, enzyme, molecule are activated.  What we do, we kind of force the system activation through this chemical and through the knowledge of these chemicals to enhance memory, and we do this very well in animals and hopefully we’ll be able to do it in people as well.

Question: What chemicals can do this?

Ottavio Arancio:  There are many chemicals that one can use to enhance memory and there are many proteins that are relevant to the process of learning and memory.  For instance, all chemicals that act on a particular gene by the name of CREB that they stimulate this gene and they can do in several different ways, are all molecules that in animals work quite well at enhancing memory. 

Question: Are these chemicals available now?

Ottavio Arancio:  No, they are.  They are available, but we can give an extra additional amount.  What we do with these chemicals, we take advantage of knowledge of what normally happens in nature and we little bit push in this.  Aiding disease is even easier because sometimes if in disease we find out one of these chemicals is less in lower amount than what it would be normally we just help the process by giving it artificially.

Question: Is Alzheimer’s inherited genetically?

Ottavio Arancio:  With respect to that I have to say that less than 5% of Alzheimer’s disease are genetically transmitted, so 95% are not genetically transmitted and generally speaking the ones that are genetically transmitted they tend to occur at earlier ages than, although it is not a general rule, but more often people who have it because of genetic reasons that 5% of the people… population have it at earlier ages, but only 5% or less than 5%, about 5, around that number.

Question: Does the likelihood of acquiring Alzheimer’s vary across cultures?

Ottavio Arancio:  It’s not that in China there is more than America or less or in Europe there is more or less than here and there, but there are particular populations that in particular circumstances that could lead to dementia and because of the habits of those you know populations.  It’s just there are small groups of people.  For instance, in the Pacific there were populations that used to eat the brain of the dead people and then they were transferring disease, which one of the symptoms of this disease was dementia and they were all developing dementia, so over there, there was a higher incidence of dementia just because this habit of eating the brain of the people that were dead the therefore like an infectious disease.  They were transferring the disease and there were higher incidence of people affected by disease.  Once this was found and this habit was stopped then the incidence of disease became the same as with in other populations.

Question: Who is most likely to get Alzheimer’s disease?

Ottavio Arancio:  In general you know if you look at our society there is not a population of people or you know that is more affected by the loss of memory.  It is a problem that hits with aging, so something related with aging and so as we age we get more memory problems.  Obviously not all people are equal.  There are some who have a better memory than others, and we do not know why some people have a better memory than others.  I mean we say that the… if we keep ourselves and our brain exercised just like a muscle then we tend to have less memory problems, so it's kind of protective the activity or mental activity.  Even some people think even physical activity it could be protective against the memory loss, you know, the loss of memory.  That’s what I would have to say.  Obviously there are diseases which are associated.  The most typical one is Alzheimer’s disease, which are associated with the loss of memory and others, but of less relevance and less…

Question: What form of memory decreases the most with aging?

Ottavio Arancio: The characteristic symptom of Alzheimer’s disease, which is really hallmark of disease, is the loss of what we call short-term memory, so that’s how the disease starts actually.  It’s people who cannot remember what they just did, just very short term memory loss and that lasts for a very, very long time and progressively the memory problem gets worse and worse and only at the very late stage or Alzheimer’s disease is when also long term memory is affected, but the major characteristic of Alzheimer’s disease, which is a very widespread disease in the population, especially at old age, is the loss of short-term memory.

Question: How do our brains create memories?

Ottavio Arancio:  Okay, the neurological process includes a series of chemical reactions at the level of the synapse and this series of reactions leads to changes in the connection of the synapses, changes that include both the…   How would you say?  Changes in the receptors that are located at the synapses such that these receptors respond in a different way and changes in the release of neurotransmitters of the synapses and eventually changes at the level of the morphology of the synapse, such that the synaptic response becomes much stronger. And even in addition to that for this memory to last long there have to be changes in the…  at the level of the genes that are part of our DNA and that are long-lasting, so there are genetic changes with formation of new proteins in the cells that will leave its, you know, like sign, its change over there, as plastic changes, like as more protein and new proteins formed at the synapse. 

You see, memory passes through several processes, several points and first you memorize something, then you consolidate this something, then you can recall it when you need to remember, then you can reconsolidate it.  It’s a process which has several steps or phases.

Question: Why are we occasionally unable to recall a particular memory?

Ottavio Arancio: I'll bet that it depends on the particular moment in which you are trying to recall that memory and certain processes that no longer happen in the brain or they are blocked.  Some chemical reactions occur and they interfere or do not occur and interfere with this process of recalling in a certain moment and then one you know has the chance then to remember it, maybe because you make an association with something at the moment that has to like…  You know if you associate something with a particular odor as an example and then that odor comes then the memory comes up.  It’s just those are tricks also to remember.

Question: Do our senses affect memory particularly strongly?

Ottavio Arancio:  Well, I mean, obviously I bet that smell is much more important for a dog than for humans—although there are humans who exercise their sense of smell and probably much better than I am to remember using smell.  I mean there is differences between sense as a way of learning according to people and we are not the same. It’s like a door that some people is more open one door than another, so or and so they use one particular way more than others, so there are differences, but if we accept through the way in which the memory gets in the chemical process that once those things get in they are very, very similar inside the brain.  They are very, very similar for different, we’ll call input of memory coming different ways, through different mechanisms and they’re very similar in humans and they are very similar between different animals.

Question: Are there any tricks to improving our ability to learn?

Ottavio Arancio:  There are ways, tricks that people use to learn for us to store more numbers that way.  It’s very important that we exercise at learning.  I bet that relying too much on your notebook or your BlackBerry or whatever does not help in this direction because we are confident that we do not need to learn, but because as I said at the beginning attention is very important, so if you do not pay enough attention because you write that kind of thing then obviously you will learn less, so the secret would be just to obviously if you will pay ten times the same thing you have more chances to learn it or if you use association within what you are learning with something else and you store this association in the brain then you will remember that particular thing better than others, so there are ways people use to memorize and then there are also…you know, differences between one person to the other.  For instance, I’m very bad with remembering numbers, but I’m much better with remembering geographical names, location, et cetera, so I bet a lot of people are better remembering notes in music than others.  It depends also what you like and what you don’t like, just because you pay more attention to what you like than to what you don’t like. 

Question: Are there any treatments available that can help improve our memories?

Ottavio Arancio:  As I said before the only thing that is sure is just to exercise your brain and just like you do with the gym with your muscles and that’s for sure it should help, because the brain…   We have to see the brain also like an organ that has a reserve, so if we build up bigger reserves then when diseases will hit or the memory problem will start occurring we’ll have more time to compensate for the problem, so diseases should be… start later and slower and just…  Not that we will avoid the disease, but it most likely what we scientists think most likely happens is just we have more reserve in the brain, so that is for sure.  I have to say also that although it needs to be confirmed, validated and one cannot dispute that it will end up like with the aluminum story that people say that diet like the Mediterranean diet with presence of antioxidant, this kind of stuff in your diet they should protect and against the problem like Alzheimer’s disease or be more protected, which does not mean again that the… does not mean that it will not happen, but it will happen…  there will be less incidence of Alzheimer’s disease in this population or a population that eats for instance, fish or…  These studies obviously we are to be careful because there are things showing it, but they might not be confirmed in the future, but that’s what I mean the exercise and eating healthy.  It’s not only memory, also other problems.

Question: What type of brain exercises are most effective?

Ottavio Arancio:  Whatever you like to do and it’s not you have to take it like a pill, now I have to do ten crossword puzzles and instead of five.  It does not… it doesn’t work like that.  It’s just to be involved with your life and being active and not…  Unfortunately when sometimes people become old they tend to be less stressed out about life and they or they tend to be depressed, so less involved, less interested, so that’s the thing is just to be active, mentally active and to be mentally active I bet you need to like what you are doing.  I mean you cannot oblige yourself to be mentally active.  I have to be mentally active.  I don’t think it works like that.

Question: How do we produce false memories?

Ottavio Arancio:  It happens in most likely you were storing things in the brain and you are confusing from maybe your fantasy with the reality and… or, one possibility.  The other possibility, like you had the wrong perception of what you saw, so you’re storing this in a way because you are convinced that it’s that way, but it was not that way.  Let’s say I make two good examples.  I mean you’re convinced that maybe you were not…  did not pay that much attention and you’re convinced that person was dressed in red instead it was pink or a color close to red then you store the thing that way.  Obviously with time the memory will become more faraway, certain aspects could disappear and we could fill them with other aspects just to fill the gap, so we make up for the memory and we build up the memory in the time of recalling the memory we are recalling stuff that occurred in other circumstances because when it’s a memory it’s not… Our brain is not a recorder like passive recorder. It’s more active processes, so being an active process there could be ways of you know changing it because actively we can change it.  That’s something which is important.  It’s not our brain is like a tape recorder or a TV or a VCR.  I mean it’s not.  It’s more active than that and there are several steps in the process of memory and recalling a memory which there are many, many steps, several steps and each one of them as a memory could be labile and could be you know changed into something else, substituted by something else.

Question: Can you explain this process?

Ottavio Arancio:  Yeah.  You have to look at memory as a process in which there are several steps which they apply some interference from.  It’s not the right word, processing of our brain of this information and this is just purely active and it’s just changed.  It’s like when you change something from analogue to digital just to make one of those things, the video from the computer and in the process of changing from analogue to digital you can change something and it would not be the same you know.  What if you change a chip or something and you change the yellow into a green, so whatever was yellow will be green and… or A, when I say an A you can even artificially change into a B if want because if you tell the computer to change all the A into a B then everything will be a B or sometimes during this process some A will change into a B then it will change.  There is some activity, something that is there occurring and it changes.