Ikerbasque News

Ikerbasque researcher: José Julio Rodríguez Arellano

We can now understand the complexity of alzheimer disease and attack it from various angles

Your research is focused on optimizing and simulating industrial processes, what does this mean?

Alzheimer's disease appears after the age of 50, which is why it was originally known as dementia praecox (early and/or pre-senile); which is characterised by the loss of memory and other cognitive mental functions at a relatively early age. There are two types of the disease: one is the genetic form – “Familial Alzheimer's Disease,” which affects only 1-2% of patients. Then there is the sporadic form, which appears at around the age of 60 and can affect anyone, whether or not their family members have Alzheimer's disease.

Alzheimer's sufferers start losing their memory. At first, this loss is very slight - they forget where they left their car keys, where they put their jacket, things that happen to most of us on occasion. Then their memory begins to deteriorate, they begin to forget who members of their family are, they don't recognise their wife, children, siblings, and although they can have moments of lucidity where they recover their memory, they gradually forget how to perform all kinds of functions, from not knowing how to get dressed (in severe cases) to not knowing how to eat. They know how to perform their bodily functions but not where to do so, they can leave the house but don't know how to come back and theses alterations appear at the most advance and severe stage of the disease.

What research are you currently carrying out at the UPV (University of the Basque Country)?
Now that we have discovered very promising results that affect different types of cells in the brain, starting next month, the next step that we're going to take here at Ikerbasque in the UPV is to carry out tests on specific treatments that, thanks to our discoveries, we believe may help patients and contribute to their recovery.  We're trying to achieve two things: to slow down the progress of the disease and its recuperation. If you examine our results you'll see they are focussed on two areas: firstly what happens at neurone level, and secondly what happens to the glia or supporting cells, of which there are two types: large cells known as macroglia and other smaller cells known as microglia.
Macroglia is composed of different cell type, but we are essentially focusing on the astrocytes which are star-shaped cells that are very important in supporting and in communications between neurones. The small cells or microglia, are defence mechanism cells within the brain and we also know that these are affected by Alzheimer’s disease.

So how is it possible to slow down the progress of the disease or reverse the process?

To a certain extent, when working on these cells, we can slow down or even recover their capacity as they tend to be affected from an early stage.  We have discovered changes in our animals from 6-9 months onwards, which is the equivalent to 50-year old humans, representing a reasonably early stage.

Meanwhile, our other line of investigation is studying what happens to the brain's ability to generate new nervous cells: the neurones, a process known as neurogenesis. This is an extremely revolutionary idea, as Doctor Santiago Ramón y Cajal's theory that once something has been born in the brain, the only possible change is for it to die, was still accepted up until 1950. The idea that nothing can be generated was, I think, the only thing that this great Maestro got wrong. Fortunately, in 1950, German researchers discovered that the brain can indeed still generate things. In fact, as we speak, both you and I are generating neurones and 80-year olds are still generating them as well. Although there are contradictory results in this respect, thanks to the kind of animal subject that we use we know that this capacity for neurogenesis is reduced in Alzheimer patients.  It occurs late at 12 months in animals, representing 60-65 years in humans, and here what we are trying to do is to recuperate it through exercise and mental activity. To a certain extent these two strategies will allow us both to delay and also to recuperate.
As of next month, we'll concentrate on trying to recuperate these alterations that we have observed. We have preliminary results, we can revert the loss of neuronal proliferation through exercise. This is one line of research.
The next line in this direction is neurone transplants. We will carry out this research in collaboration with colleagues in the Czech Republic. At glia level, what happens is atrophy, which we would define as cells becoming smaller, losing their ramifications and therefore their ability to carry out their functions, and the idea is to administer certain kinds of tissue nutrition, certain factors to our model, that will make the cell return to its correct form with all of its prolongations to maintain the structure. These are the two fundamental lines that we're going to follow. Moreover, neural transplants have not yet been carried out in our model, we'll be the first in the country to do so.

How important are the discoveries that the working group formed by you and Dr. Alexei Verkhratsky have made for medical science and what might these mean for the Basque Country?

I think it could be revolutionary for the Basque Country and the Scientific Community in the Basque Country as, in fact, in Spain we are the only team to use this animal model that we have imported from England and of which we now have a colony functioning here. It would place us at the forefront of research into Alzheimer's in the country and in the Autonomous Regions, as we are essentially concentrating not only on our animal model, but also on glial alterations that have only been observed by a few people whose observations have been totally opposite to what we have seen. I think it will be an enormous stimulus for Basque science that will then have repercussions for national research.

Can you put a date on an effective and reversible treatment for this disease?

Unfortunately no. Perhaps what’s interesting is to try and focus on the fact that the discovery of all these new components helps us to improve our understanding of the disease and therefore it is much easier to follow a particular line of enquiry or to combine such lines of research to discover effective treatments. To focus not just on the neurones, but to consider the glia as well.
You cannot say that we're going to cure Alzheimer's tomorrow. I couldn't hope for anything more! But no one knows if we're ever going to find a cure.
You give people hope in that now we're beginning to understand the disease we’re beginning to have more perspectives on how it works. Now that we know that the illness affects the glial cells as well as the neurones, we can understand the complexity of the disease and attack it from various angles, which is something that we couldn't do before.

The point of our work is to be able, in the early phases of the illness, to administer something that, although we cannot be sure will prevent Alzheimer’s completely, then at least we know it will considerably delay its progress and improve quality of life and even, with a bit of luck maybe we'll discover that we can stop it. That's what we're working on.