How Memories Are Made, and Lost

A protein that scientists once thought was a "piece of garbage in the brain" turns out to play a key role in memory formation. At high concentrations, however, it spells “the beginning of the end for memory.”
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TRANSCRIPT

Question: What is the goal of your research? 

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: How does this protein contribute 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?