Big Think Interview With Ottavio Arancio
Dr Arancio is a cellular neurobiologist who has contributed to the characterization of the mechanisms of learning in both normal conditions and during neurodegenerative diseases. During the past decade he has pioneered the field of mechanisms of synaptic dysfunction in Alzheimer’s disease. Dr. Arancio’s laboratory has focused primarily on events triggered by amyloid protein. These studies, which have suggested new links between synaptic dysfunction and amyloid protein, are of a general relevance to the field of Alzheimer’s disease both for understanding the etiopathogenesis of the disease and for developing therapies aiming to improve the cognitive symptoms.
Question: Can you describe your research into Alzheimer’s disease?\r\n\r\n
Ottavio Arancio: \r\nOkay, the overall goal of the research in my lab is to find a therapy\r\nagainst the Alzheimer’s disease. \r\nThat’s a very general way of saying things and to be more specific we\r\nare… we have different strategies in the lab to go to achieve this goal, so we\r\nare trying to approach it from different perspectives and if I have to\r\nsummarize these perspectives in a few words I should say that in one kind of\r\nstudies we are trying to understand what is the function of a molecule that is\r\ncalled beta amyloid and this is a molecule made by many amino acids. Once there are many amino acids\r\ntogether those molecules are called peptides. Anyway, this beta amyloid, which is produced in a very high\r\namount in the brain of people with this disease and is known also to be very\r\ntoxic to the communication of the cells in the brain and therefore to lead to\r\nmemory impairment, so but we know that this molecule is present in the brain of\r\npeople throughout life, just normal half the people and it is there in very low\r\namount and nobody knew what was the function, if at all to any function this\r\nprotein in this very low amount. \r\nWhat most of scientists thought was that it was kind of piece of garbage\r\nin the brain of people with no relevance whatsoever and instead we have started\r\nworking on it and we have found that actually probably the very likely function\r\nof this protein in very low amount is just to be there to lead to normal\r\nmemory, so without it we cannot store information in the brain, we cannot learn\r\nand there will not be normal memory.\r\n\r\n
So I mean with all the study what we think is that this\r\nmolecule is there. It’s necessary\r\nfor memory and then for some unknown reason we start making… people with the disease start making a lot\r\nof it and the fact there is a lot just makes opposite of what it does in the\r\nnormal brain, so it’s actually it reduces memory when it is there in a very\r\nhigh amount and so this is a very, very you know interesting characteristic and\r\nwe think that actually until the studies were not there what people were doing\r\nto understand the cause of the disease was just to look at the disease from the\r\nvery end of it instead of trying to understand… You know it was a kind of a piece of a puzzle that is\r\nmissing to understand the… to understand how something which is there becomes\r\nwhat is the beginning of the end for memory. So in other words just to make things more simple because\r\notherwise we get lost here is that now we know that normal function of this\r\nprotein in very low amount in the brain is to lead to memories, that this\r\nmolecule is necessary for memory and that we now need to understand how the\r\nproblem starts, how memory is impaired. \r\nWe need to understand how this normal regulation of the level of this\r\nprotein in the brain is broken and so the brain starts to make a lot of\r\nit. So we think that through this\r\nstudy and through establishing what is normal function of the protein we could\r\nunderstand at the very beginning of the disease and once you usually understand\r\nhow this starts, which is something which we really do not have it so far.\r\n\r\n
\r\n\r\n Question: Can you explain how this protein contributes to\r\nmemory loss?
Question: Can you explain how this protein contributes to\r\nmemory loss?
Ottavio Arancio: What I found is that the normal function of this protein is\r\nthere to lead to memory, the opposite of memory loss. So now I would like to understand the bridge between the\r\nnormal function of this protein, which is just to lead to memory to its\r\nabnormal function, which is the memory loss. You see, so the fact that the protein gives to memory loss\r\nis something that was already known by scientists. It’s slightly different. I don’t want to take credit of something I did not\r\ndiscover. What I have discovered\r\nis that this protein in normal low concentration leads to memory. It leads to memory loss the opposite\r\nonly when it is there in very high amount, and I would like to bridge the gap\r\nbetween its normal function and its pathological function, its bad\r\nfunction. How does a good turn\r\ninto a bad guy? How does a good\r\nprotein turn into a bad protein?\r\n\r\n
Question: What factors affect our memory?\r\n\r\n
Ottavio\r\nArancio: One of the biggest\r\nfactors that can affect it is attention for instance. I mean if you do not pay attention to something it’s very\r\nlikely that you will learn what you have… yeah, what you just saw. For instance, just to make an example I\r\nbet that many people… many of us remember what we did on September 11 because\r\nyou know there was a coincidence of just we paid particular attention to all\r\nwhat happened that day. I bet that\r\nmuch less people will remember what happened the day before or 2 days\r\nbefore. So that’s… attention is\r\nalso… is very, very important. \r\nAnother factor that is very important would be motivation to… If you don’t care about doing something\r\nyou will not learn about it if you are depressed or things like that, you will\r\nnot learn what you just saw, what you just did. You will not memorize what you just did. Obviously you need to be able to\r\nperceive the stimulus. If you\r\ncannot see, no way that you will remember or if you do not hear you cannot\r\nremember words. So we need to be\r\nable to get to those things. This\r\nis stuff that we…help remembering. \r\nObviously those are not the only things because we can monitor also\r\nthrough chemicals and other ways also memories and hopefully in the future\r\nwe’ll be even better at that. So\r\nwe can also stimulate memory chemically.\r\n\r\n
Question: How do memory enhancing chemicals work?\r\n\r\n
Ottavio\r\nArancio: What they do, they\r\nwill work at the level of the synaptic connection and since at the time of\r\nmemory there is a chain of chemical reaction at the level of the synapse, but\r\nchemical means the same…protein, enzyme, molecule are activated. What we do, we kind of force the system\r\nactivation through this chemical and through the knowledge of these chemicals to\r\nenhance memory, and we do this very well in animals and hopefully we’ll be able\r\nto do it in people as well.\r\n\r\n
Question: What chemicals can do this?\r\n\r\n
Ottavio\r\nArancio: There are many\r\nchemicals that one can use to enhance memory and there are many proteins that\r\nare relevant to the process of learning and memory. For instance, all chemicals that act on a particular gene by\r\nthe name of CREB that they stimulate this gene and they can do in several\r\ndifferent ways, are all molecules that in animals work quite well at enhancing\r\nmemory.\r\n\r\n
Question: Are these chemicals available now?\r\n\r\n
Ottavio\r\nArancio: No, they are. They are available, but we can give an\r\nextra additional amount. What we\r\ndo with these chemicals, we take advantage of knowledge of what normally happens\r\nin nature and we little bit push in this. \r\nAiding disease is even easier because sometimes if in disease we find\r\nout one of these chemicals is less in lower amount than what it would be\r\nnormally we just help the process by giving it artificially.\r\n\r\n
Question: Is Alzheimer’s inherited genetically?\r\n\r\n
Ottavio\r\nArancio: With respect to\r\nthat I have to say that less than 5% of Alzheimer’s disease are genetically\r\ntransmitted, so 95% are not genetically transmitted and generally speaking the\r\nones that are genetically transmitted they tend to occur at earlier ages than,\r\nalthough it is not a general rule, but more often people who have it because of\r\ngenetic reasons that 5% of the people… population have it at earlier ages, but\r\nonly 5% or less than 5%, about 5, around that number.\r\n\r\n
\r\n\r\n Question: Does the likelihood of acquiring Alzheimer’s vary\r\nacross cultures?
Question: Does the likelihood of acquiring Alzheimer’s vary\r\nacross cultures?
\r\n\r\n Ottavio\r\nArancio: It’s not that in\r\nChina there is more than America or less or in Europe there is more or less\r\nthan here and there, but there are particular populations that in particular\r\ncircumstances that could lead to dementia and because of the habits of those\r\nyou know populations. It’s just\r\nthere are small groups of people. \r\nFor instance, in the Pacific there were populations that used to eat the\r\nbrain of the dead people and then they were transferring disease, which one of\r\nthe symptoms of this disease was dementia and they were all developing\r\ndementia, so over there, there was a higher incidence of dementia just because\r\nthis habit of eating the brain of the people that were dead the therefore like\r\nan infectious disease. They were\r\ntransferring the disease and there were higher incidence of people affected by\r\ndisease. Once this was found and\r\nthis habit was stopped then the incidence of disease became the same as with in\r\nother populations.
Ottavio\r\nArancio: It’s not that in\r\nChina there is more than America or less or in Europe there is more or less\r\nthan here and there, but there are particular populations that in particular\r\ncircumstances that could lead to dementia and because of the habits of those\r\nyou know populations. It’s just\r\nthere are small groups of people. \r\nFor instance, in the Pacific there were populations that used to eat the\r\nbrain of the dead people and then they were transferring disease, which one of\r\nthe symptoms of this disease was dementia and they were all developing\r\ndementia, so over there, there was a higher incidence of dementia just because\r\nthis habit of eating the brain of the people that were dead the therefore like\r\nan infectious disease. They were\r\ntransferring the disease and there were higher incidence of people affected by\r\ndisease. Once this was found and\r\nthis habit was stopped then the incidence of disease became the same as with in\r\nother populations.
Question: Who is most\r\nlikely to get Alzheimer’s disease?\r\n\r\n
Ottavio\r\nArancio: In general you know if you\r\nlook at our society there is not a population of people or you know that is\r\nmore affected by the loss of memory. \r\nIt is a problem that hits with aging, so something related with aging\r\nand so as we age we get more memory problems. Obviously not all people are equal. There are some who have a better memory\r\nthan others, and we do not know why some people have a better memory than\r\nothers. I mean we say that the… if\r\nwe keep ourselves and our brain exercised just like a muscle then we tend to\r\nhave less memory problems, so it's kind of protective the\r\nactivity or mental activity. Even\r\nsome people think even physical activity it could be protective against the\r\nmemory loss, you know, the loss of memory. \r\nThat’s what I would have to say. \r\nObviously there are diseases which are associated. The most typical one is Alzheimer’s\r\ndisease, which are associated with the loss of memory and others, but of less\r\nrelevance and less…\r\n\r\n
Question: What form of memory decreases the most with aging?\r\n\r\n
Ottavio\r\nArancio: The characteristic symptom of Alzheimer’s disease, which is\r\nreally hallmark of disease, is the loss of what we call short-term memory, so\r\nthat’s how the disease starts actually. \r\nIt’s people who cannot remember what they just did, just very short term\r\nmemory loss and that lasts for a very, very long time and progressively the\r\nmemory problem gets worse and worse and only at the very late stage or Alzheimer’s\r\ndisease is when also long term memory is affected, but the major characteristic\r\nof Alzheimer’s disease, which is a very widespread disease in the population,\r\nespecially at old age, is the loss of short-term memory.\r\n\r\n
Question: How do our brains create memories?\r\n\r\n
Ottavio\r\nArancio: Okay, the\r\nneurological process includes a series of chemical reactions at the level of\r\nthe synapse and this series of reactions leads to changes in the connection of\r\nthe synapses, changes that include both the… How would you say? Changes in the receptors that are located at the synapses\r\nsuch that these receptors respond in a different way and changes in the release\r\nof neurotransmitters of the synapses and eventually changes at the level of the\r\nmorphology 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\r\nof our DNA and that are long-lasting, so there are genetic changes with\r\nformation of new proteins in the cells that will leave its, you know, like sign,\r\nits change over there, as plastic changes, like as more protein and new proteins\r\nformed at the synapse.You see, memory\r\npasses through several processes, several points and first you memorize\r\nsomething, then you consolidate this something, then you can recall it when you\r\nneed to remember, then you can reconsolidate it. It’s a process which has several steps or phases.\r\n\r\n
Question: Why are we occasionally unable to recall a\r\nparticular memory?\r\n\r\n
\r\n\r\n Ottavio\r\nArancio: I'll bet that it depends on the particular moment in which you are\r\ntrying to recall that memory and certain processes that no longer happen in the\r\nbrain or they are blocked. Some\r\nchemical reactions occur and they interfere or do not occur and interfere with\r\nthis process of recalling in a certain moment and then one you know has the\r\nchance then to remember it, maybe because you make an association with\r\nsomething at the moment that has to like… \r\nYou know if you associate something with a particular odor as an example\r\nand then that odor comes then the memory comes up. It’s just those are tricks also to remember.
Ottavio\r\nArancio: I'll bet that it depends on the particular moment in which you are\r\ntrying to recall that memory and certain processes that no longer happen in the\r\nbrain or they are blocked. Some\r\nchemical reactions occur and they interfere or do not occur and interfere with\r\nthis process of recalling in a certain moment and then one you know has the\r\nchance then to remember it, maybe because you make an association with\r\nsomething at the moment that has to like… \r\nYou know if you associate something with a particular odor as an example\r\nand 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?\r\n\r\n
Ottavio\r\nArancio: Well, I mean,\r\nobviously 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\r\nbetter than I am to remember using smell. \r\nI mean there is differences between sense as a way of learning according\r\nto people and we are not the same. It’s like a door that some people is more\r\nopen one door than another, so or and so they use one particular way more than\r\nothers, so there are differences, but if we accept through the way in which the\r\nmemory gets in the chemical process that once those things get in they are\r\nvery, very similar inside the brain. \r\nThey are very, very similar for different, we’ll call input of memory\r\ncoming different ways, through different mechanisms and they’re very similar in\r\nhumans and they are very similar between different animals.\r\n\r\n
Question: Are there any tricks to improving our ability to\r\nlearn?\r\n\r\n
Ottavio\r\nArancio: There are ways,\r\ntricks that people use to learn for us to store more numbers that way. It’s very important that we exercise at\r\nlearning. I bet that relying too\r\nmuch on your notebook or your BlackBerry or whatever does not help in this\r\ndirection because we are confident that we do not need to learn, but because as\r\nI said at the beginning attention is very important, so if you do not pay\r\nenough attention because you write that kind of thing then obviously you will\r\nlearn less, so the secret would be just to obviously if you will pay ten times\r\nthe same thing you have more chances to learn it or if you use association\r\nwithin what you are learning with something else and you store this association\r\nin the brain then you will remember that particular thing better than others,\r\nso there are ways people use to memorize and then there are also…you know,\r\ndifferences between one person to the other. For instance, I’m very bad with remembering numbers, but I’m\r\nmuch better with remembering geographical names, location, et cetera, so I bet a\r\nlot of people are better remembering notes in music than others. It depends also what you like and what\r\nyou don’t like, just because you pay more attention to what you like than to\r\nwhat you don’t like.\r\n\r\n
Question: Are there any treatments available that can\r\nhelp improve our memories?\r\n\r\n
Ottavio\r\nArancio: As I said before\r\nthe only thing that is sure is just to exercise your brain and just like you do\r\nwith the gym with your muscles and that’s for sure it should help, because the\r\nbrain… We have to see the\r\nbrain also like an organ that has a\r\nreserve, so if we build up bigger reserves then when diseases will hit or the memory\r\nproblem will start occurring we’ll have more time to compensate for the\r\nproblem, so diseases should be… start later and slower and just… Not that we will avoid the disease, but\r\nit most likely what we scientists think most likely happens is just we have\r\nmore reserve in the brain, so that is for sure. I have to say also that although it needs to be confirmed,\r\nvalidated and one cannot dispute that it will end up like with the aluminum\r\nstory that people say that diet like the Mediterranean diet with presence of\r\nantioxidant, this kind of stuff in your diet they should protect and against\r\nthe problem like Alzheimer’s disease or be more protected, which does not mean\r\nagain that the… does not mean that it will not happen, but it will happen… there will be less incidence of Alzheimer’s\r\ndisease in this population or a population that eats for instance, fish\r\nor… These studies obviously we are\r\nto be careful because there are things showing it, but they might not be\r\nconfirmed in the future, but that’s what I mean the exercise and eating\r\nhealthy. It’s not only memory,\r\nalso other problems.\r\n\r\n
Question: What type of brain exercises are most effective?\r\n\r\n
Ottavio\r\nArancio: Whatever you like\r\nto do and it’s not you have to take it like a pill, now I have to do ten\r\ncrossword puzzles and instead of five. \r\nIt does not… it doesn’t work like that. It’s just to be involved with your life and being active and\r\nnot… Unfortunately when sometimes\r\npeople become old they tend to be less stressed out about life and they or they\r\ntend to be depressed, so less involved, less interested, so that’s the thing is\r\njust to be active, mentally active and to be mentally active I bet you need to\r\nlike what you are doing. I mean\r\nyou cannot oblige yourself to be mentally active. I have to be mentally active. I don’t think it works like that.\r\n\r\n
Question: How do we produce false memories?\r\n\r\n
Ottavio\r\nArancio: It happens in most\r\nlikely you were storing things in the brain and you are confusing from maybe\r\nyour fantasy with the reality and… or, one possibility. The other possibility, like you had the\r\nwrong perception of what you saw, so you’re storing this in a way because you\r\nare convinced that it’s that way, but it was not that way. Let’s say I make two good\r\nexamples. I mean you’re convinced\r\nthat maybe you were not… did not\r\npay that much attention and you’re convinced that person was dressed in red\r\ninstead it was pink or a color close to red then you store the thing that\r\nway. Obviously with time the\r\nmemory will become more faraway, certain aspects could disappear and we could\r\nfill them with other aspects just to fill the gap, so we make up for the memory\r\nand we build up the memory in the time of recalling the memory we are recalling\r\nstuff that occurred in other circumstances because when it’s a memory it’s not…\r\nOur brain is not a recorder like passive recorder. It’s more active processes,\r\nso being an active process there could be ways of you know changing it because\r\nactively we can change it. That’s\r\nsomething which is important. It’s\r\nnot 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\r\nare several steps in the process of memory and recalling a memory which there\r\nare many, many steps, several steps and each one of them as a memory could be\r\nlabile and could be you know changed into something else, substituted by\r\nsomething else.\r\n\r\n
Question: Can you explain this process?\r\n\r\n
Ottavio\r\nArancio: Yeah. You have to look at memory as a process\r\nin which there are several steps which they apply some interference from. It’s not the right word, processing of\r\nour brain of this information and this is just purely active and it’s just\r\nchanged. It’s like when you change\r\nsomething from analogue to digital just to make one of those things, the video\r\nfrom the computer and in the process of changing from analogue to digital you\r\ncan change something and it would not be the same you know. What if you change a chip or something\r\nand you change the yellow into a green, so whatever was yellow will be green\r\nand… or A, when I say an A you can even artificially change into a B if want\r\nbecause if you tell the computer to change all the A into a B then everything\r\nwill be a B or sometimes during this process some A will change into a B then\r\nit will change. There is some\r\nactivity, something that is there occurring and it changes.\r\n\r\n\r\n\r\n\r\n
A conversation with the professor at the Taub Institute for Research in Alzheimer's Disease and the Aging Brain at Columbia University.
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