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

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Ottavio Arancio: rnOkay, the overall goal of the research in my lab is to find a therapyrnagainst the Alzheimer’s disease. rnThat’s a very general way of saying things and to be more specific wernare… we have different strategies in the lab to go to achieve this goal, so wernare trying to approach it from different perspectives and if I have tornsummarize these perspectives in a few words I should say that in one kind ofrnstudies we are trying to understand what is the function of a molecule that isrncalled beta amyloid and this is a molecule made by many amino acids.  Once there are many amino acidsrntogether those molecules are called peptides.  Anyway, this beta amyloid, which is produced in a very highrnamount in the brain of people with this disease and is known also to be veryrntoxic to the communication of the cells in the brain and therefore to lead tornmemory impairment, so but we know that this molecule is present in the brain ofrnpeople throughout life, just normal half the people and it is there in very lowrnamount and nobody knew what was the function, if at all to any function thisrnprotein in this very low amount. rnWhat most of scientists thought was that it was kind of piece of garbagernin the brain of people with no relevance whatsoever and instead we have startedrnworking on it and we have found that actually probably the very likely functionrnof this protein in very low amount is just to be there to lead to normalrnmemory, so without it we cannot store information in the brain, we cannot learnrnand there will not be normal memory. 

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So I mean with all the study what we think is that thisrnmolecule is there.  It’s necessaryrnfor memory and then for some unknown reason we start making…  people with the disease start making a lotrnof it and the fact there is a lot just makes opposite of what it does in thernnormal brain, so it’s actually it reduces memory when it is there in a veryrnhigh amount and so this is a very, very you know interesting characteristic andrnwe think that actually until the studies were not there what people were doingrnto understand the cause of the disease was just to look at the disease from thernvery end of it instead of trying to understand…  You know it was a kind of a piece of a puzzle that isrnmissing to understand the… to understand how something which is there becomesrnwhat is the beginning of the end for memory.  So in other words just to make things more simple becausernotherwise we get lost here is that now we know that normal function of thisrnprotein in very low amount in the brain is to lead to memories, that thisrnmolecule is necessary for memory and that we now need to understand how thernproblem starts, how memory is impaired. rnWe need to understand how this normal regulation of the level of thisrnprotein in the brain is broken and so the brain starts to make a lot ofrnit.  So we think that through thisrnstudy and through establishing what is normal function of the protein we couldrnunderstand at the very beginning of the disease and once you usually understandrnhow this starts, which is something which we really do not have it so far.

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Question: Can you explain how this protein contributes tornmemory loss?

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

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Question: What factors affect our memory?

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OttaviornArancio:  One of the biggestrnfactors that can affect it is attention for instance.  I mean if you do not pay attention to something it’s veryrnlikely that you will learn what you have… yeah, what you just saw.  For instance, just to make an example Irnbet that many people… many of us remember what we did on September 11 becausernyou know there was a coincidence of just we paid particular attention to allrnwhat happened that day.  I bet thatrnmuch less people will remember what happened the day before or 2 daysrnbefore.  So that’s… attention isrnalso… is very, very important. rnAnother factor that is very important would be motivation to…  If you don’t care about doing somethingrnyou will not learn about it if you are depressed or things like that, you willrnnot learn what you just saw, what you just did.  You will not memorize what you just did.  Obviously you need to be able tornperceive the stimulus.  If yourncannot see, no way that you will remember or if you do not hear you cannotrnremember words.  So we need to bernable to get to those things.  Thisrnis stuff that we…help remembering. rnObviously those are not the only things because we can monitor alsornthrough chemicals and other ways also memories and hopefully in the futurernwe’ll be even better at that.  Sornwe can also stimulate memory chemically. 

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Question: How do memory enhancing chemicals work?

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OttaviornArancio:  What they do, theyrnwill work at the level of the synaptic connection and since at the time ofrnmemory there is a chain of chemical reaction at the level of the synapse, butrnchemical means the same…protein, enzyme, molecule are activated.  What we do, we kind of force the systemrnactivation through this chemical and through the knowledge of these chemicals tornenhance memory, and we do this very well in animals and hopefully we’ll be ablernto do it in people as well.

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Question: What chemicals can do this?

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OttaviornArancio: There are manyrnchemicals that one can use to enhance memory and there are many proteins thatrnare relevant to the process of learning and memory.  For instance, all chemicals that act on a particular gene byrnthe name of CREB that they stimulate this gene and they can do in severalrndifferent ways, are all molecules that in animals work quite well at enhancingrnmemory. 

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Question: Are these chemicals available now?

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OttaviornArancio: No, they are.  They are available, but we can give anrnextra additional amount.  What werndo with these chemicals, we take advantage of knowledge of what normally happensrnin nature and we little bit push in this. rnAiding disease is even easier because sometimes if in disease we findrnout one of these chemicals is less in lower amount than what it would bernnormally we just help the process by giving it artificially.

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Question: Is Alzheimer’s inherited genetically?

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

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

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OttaviornArancio:  It’s not that inrnChina there is more than America or less or in Europe there is more or lessrnthan here and there, but there are particular populations that in particularrncircumstances that could lead to dementia and because of the habits of thosernyou know populations.  It’s justrnthere are small groups of people. rnFor instance, in the Pacific there were populations that used to eat thernbrain of the dead people and then they were transferring disease, which one ofrnthe symptoms of this disease was dementia and they were all developingrndementia, so over there, there was a higher incidence of dementia just becausernthis habit of eating the brain of the people that were dead the therefore likernan infectious disease.  They wererntransferring the disease and there were higher incidence of people affected byrndisease.  Once this was found andrnthis habit was stopped then the incidence of disease became the same as with inrnother populations.

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Question: Who is mostrnlikely to get Alzheimer’s disease?

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OttaviornArancio:  In general you know if yournlook at our society there is not a population of people or you know that isrnmore affected by the loss of memory. rnIt is a problem that hits with aging, so something related with agingrnand so as we age we get more memory problems.  Obviously not all people are equal.  There are some who have a better memoryrnthan others, and we do not know why some people have a better memory thanrnothers.  I mean we say that the… ifrnwe keep ourselves and our brain exercised just like a muscle then we tend tornhave less memory problems, so it's kind of protective thernactivity or mental activity.  Evenrnsome people think even physical activity it could be protective against thernmemory loss, you know, the loss of memory. rnThat’s what I would have to say. rnObviously there are diseases which are associated.  The most typical one is Alzheimer’srndisease, which are associated with the loss of memory and others, but of lessrnrelevance and less…

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

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

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Question: How do our brains create memories?

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

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

Question: Why are we occasionally unable to recall arnparticular memory?

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OttaviornArancio: I'll bet that it depends on the particular moment in which you arerntrying to recall that memory and certain processes that no longer happen in thernbrain or they are blocked.  Somernchemical reactions occur and they interfere or do not occur and interfere withrnthis process of recalling in a certain moment and then one you know has thernchance then to remember it, maybe because you make an association withrnsomething at the moment that has to like… rnYou know if you associate something with a particular odor as an examplernand then that odor comes then the memory comes up.  It’s just those are tricks also to remember.

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Question: Do our senses affect memory particularly strongly?

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OttaviornArancio: Well, I mean,rnobviously 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 muchrnbetter than I am to remember using smell. rnI mean there is differences between sense as a way of learning accordingrnto people and we are not the same. It’s like a door that some people is morernopen one door than another, so or and so they use one particular way more thanrnothers, so there are differences, but if we accept through the way in which thernmemory gets in the chemical process that once those things get in they arernvery, very similar inside the brain. rnThey are very, very similar for different, we’ll call input of memoryrncoming different ways, through different mechanisms and they’re very similar inrnhumans and they are very similar between different animals.

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

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OttaviornArancio: There are ways,rntricks that people use to learn for us to store more numbers that way.  It’s very important that we exercise atrnlearning.  I bet that relying toornmuch on your notebook or your BlackBerry or whatever does not help in thisrndirection because we are confident that we do not need to learn, but because asrnI said at the beginning attention is very important, so if you do not payrnenough attention because you write that kind of thing then obviously you willrnlearn less, so the secret would be just to obviously if you will pay ten timesrnthe same thing you have more chances to learn it or if you use associationrnwithin what you are learning with something else and you store this associationrnin the brain then you will remember that particular thing better than others,rnso there are ways people use to memorize and then there are also…you know,rndifferences between one person to the other.  For instance, I’m very bad with remembering numbers, but I’mrnmuch better with remembering geographical names, location, et cetera, so I bet arnlot of people are better remembering notes in music than others.  It depends also what you like and whatrnyou don’t like, just because you pay more attention to what you like than tornwhat you don’t like. 

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

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OttaviornArancio:  As I said beforernthe only thing that is sure is just to exercise your brain and just like you dornwith the gym with your muscles and that’s for sure it should help, because thernbrain…   We have to see thernbrain also like an organ that has arnreserve, so if we build up bigger reserves then when diseases will hit or the memoryrnproblem will start occurring we’ll have more time to compensate for thernproblem, so diseases should be… start later and slower and just…  Not that we will avoid the disease, butrnit most likely what we scientists think most likely happens is just we havernmore reserve in the brain, so that is for sure.  I have to say also that although it needs to be confirmed,rnvalidated and one cannot dispute that it will end up like with the aluminumrnstory that people say that diet like the Mediterranean diet with presence ofrnantioxidant, this kind of stuff in your diet they should protect and againstrnthe problem like Alzheimer’s disease or be more protected, which does not meanrnagain that the… does not mean that it will not happen, but it will happen…  there will be less incidence of Alzheimer’srndisease in this population or a population that eats for instance, fishrnor…  These studies obviously we arernto be careful because there are things showing it, but they might not bernconfirmed in the future, but that’s what I mean the exercise and eatingrnhealthy.  It’s not only memory,rnalso other problems.

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Question: What type of brain exercises are most effective?

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OttaviornArancio: Whatever you likernto do and it’s not you have to take it like a pill, now I have to do tenrncrossword puzzles and instead of five. rnIt does not… it doesn’t work like that.  It’s just to be involved with your life and being active andrnnot…  Unfortunately when sometimesrnpeople become old they tend to be less stressed out about life and they or theyrntend to be depressed, so less involved, less interested, so that’s the thing isrnjust to be active, mentally active and to be mentally active I bet you need tornlike what you are doing.  I meanrnyou cannot oblige yourself to be mentally active.  I have to be mentally active.  I don’t think it works like that.

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Question: How do we produce false memories?

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OttaviornArancio:  It happens in mostrnlikely you were storing things in the brain and you are confusing from maybernyour fantasy with the reality and… or, one possibility.  The other possibility, like you had thernwrong perception of what you saw, so you’re storing this in a way because yournare convinced that it’s that way, but it was not that way.  Let’s say I make two goodrnexamples.  I mean you’re convincedrnthat maybe you were not…  did notrnpay that much attention and you’re convinced that person was dressed in redrninstead it was pink or a color close to red then you store the thing thatrnway.  Obviously with time thernmemory will become more faraway, certain aspects could disappear and we couldrnfill them with other aspects just to fill the gap, so we make up for the memoryrnand we build up the memory in the time of recalling the memory we are recallingrnstuff that occurred in other circumstances because when it’s a memory it’s not…rnOur brain is not a recorder like passive recorder. It’s more active processes,rnso being an active process there could be ways of you know changing it becausernactively we can change it.  That’srnsomething which is important.  It’srnnot 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 therernare several steps in the process of memory and recalling a memory which therernare many, many steps, several steps and each one of them as a memory could bernlabile and could be you know changed into something else, substituted byrnsomething else.

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Question: Can you explain this process?

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

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