October 25, 2021

I, Science

The science magazine of Imperial College

Alzheimer's update: an interview with researcher Dr Magdalena Sastre
Progression of Alzheimer’s disease. Neuronal death and the formation of neurofibrillary tangles and beta-amyloid plaques.

Magdalena Sastre is a senior lecturer at Imperial College London in the division of Brain Sciences. Her research forcuses on the molecular mechanisms behind Alzheimer’s disease. In the Time issue of I, Science, we wanted to ask her how time can affect our brains, in terms of the consequences of age-related disease and how we can try to treat or prevent neurodegenerative disease.

So, what happens to our brains when we age?

When we age, we lose neurons and the brain usually shrinks. This is in a normal ageing population. But in cases of Alzheimer’s disease this atrophy in the brain is more pronounced, and people lose neurons in certain areas of the brain that are involved in learning, reasoning and in orientation like the hippocampus or the cortex.

Can you tell me about some of the molecular mechanisms behind Alzheimer’s disease?

Astrocytes, a type of glial cell, are the most abundant cell in the human brain

In the brain of an Alzheimer’s patient, we have the deposition of certain proteins. One is called amyloid beta protein that makes amyloid plaques, and other is phosphorylated tau that aggregates inside the neurons and the neurons tend to die. In the brain of these patients, surrounding these [amyloid] plaques there are glial cells – support cells that can secrete inflammatory mediators. These inflammatory mediators could mediate neuronal death, and many people believe that this is the way that amyloid is toxic for the neurons and responsible for the neurodegeneration that occurs in the brains of these patients.

What kind of research are you doing at the moment?

We are doing two kinds of research. One is in vitro research, using cell lines, and we are trying to investigate the mechanisms and pathways by which inflammation affects the formation of amyloid and neuronal death. And on the other hand, we are using animal models in which we are trying different therapies to see which one could be effective for treating the disease. And many of these therapies are anti-inflammatory therapies.

Any promising results?

Structure of the FGF2 protein

Yes, our last paper was on a growth factor called FGF2, or fibroblast growth factor, and we have seen that the animals treated with this growth factor, have improved memory and reduced pathology.

How much can environmental factors influence the development of Alzheimer’s disease?

There are certain environmental factors, like brain trauma or type-2 diabetes that could affect the increase of inflammation, so we are trying to find out if these could affect the progression of the disease.

What is the best way to prevent Alzheimer’s disease?

There are lifestyle factors that are very important, like doing exercise and eating the right food. Smoking is also dangerous for the brain, as is drinking alcohol. The most protective factor for Alzheimer’s disease is physical exercise: it’s not only good for your heart, it’s also good for your brain!

You can do the basic research, but policy is obviously needed to implement it effectively. What can policymakers do to help reduce Alzheimer’s disease?

There are two things they can do, they can give more money for research, not only for translational research to find the medicines to cure Alzheimer’s, but also to investigate the cause of Alzheimer’s. That is what we are doing in my lab, basic science research. And the other thing is to try to get people to improve their lifestyle and make people aware that when they have some symptoms of dementia they should go to the neurologist or the psychiatrist because the sooner they get diagnosed the better.

How important is early diagnosis?

Alzheimers_brainThey are investing a lot of money in early diagnosis because unfortunately all the clinical trials that have been done so far have been done in severely ill Alzheimer’s patients, when they have lost a lot of neurons. And the neurons do not regenerate. So if you can stop the progression of the disease at earlier stages with an early diagnosis of the disease, for instance using imaging, or with analysis of biomarkers in the blood, or the CSF [cerebrospinal fluid], then people could get treatment earlier, to have more chance of not getting worse.

Why is it so important to research these diseases?

There are several reasons. One is to know which is the cause of the disease. If we know the cause of the disease or what provokes Alzheimer’s, it will be much easier to find a treatment for the disease. Unfortunately Alzheimer’s, Parkinson’s and other neurological diseases don’t have a cure. They just have some treatments that ameliorate the symptoms but they don’t cure the disease, so we need to find better treatments. And secondly because all these diseases are caused when people get older. And now the population in the world is ageing, so it’s very normal to find people that are 80, 90 years of age, and the probability of getting Alzheimer’s at this age is almost 40% so we need to stop this because it generates an enormous cost.

How important is the inter-disciplinary approach of getting clinicians and researchers working together?

It’s very important because you have to work closely with the patients to see if your results are reflected in an Alzheimer’s patient. It’s very important if we have a treatment that we have shown that works in animals and in cells that it’s also working in humans, because we are very different. So we need to interact with the clinicians and organise clinical trials with them.

What is the most important question in neuroscience?

In my field of research I think the most important question is to see how we can stop neurodegeneration because so far nobody has managed to do that and it affects not only Alzheimer’s disease (my field) but other neurological diseases like multiple sclerosis, Parkinson’s disease or ALS [amyotrophic lateral sclerosis]. So I think if we try to find out why the neurons degenerate and how to stop that, that will be the future for all these kinds of diseases.

What is your favourite part of your work?

I like working in the lab because even though I am a lecturer, and I’m supposed to be in my office writing grants, I also like doing experiments – it’s like cooking – and it’s very exciting when you have a very good result and you think “we’re going to publish this in a very good journal!”

Iona Twaddell is studying for an MSc in Science Communication

Images: Alzheimer’s disease neuronal death gif ; astrocyte; FGF2 structure; brain comparison (all Wikimedia Commons)