"The treatment is too late"

17.09.2019 – The molecular biologist from Munich, Prof. dr. Christian Haass is one of the most renowned researchers of Alzheimer's in the world. For his work on the development of the disease, he received the Brain Award, which is considered by brain researchers as similar to the Nobel Prize. On September 30, the 59-year-old will also receive the "DZNE Hartwig Piepenbrock Prize" worth € 60,000 – for innovative information on the mechanisms of dementia. Haass is the spokesperson for the Munich site of the German Center for Neurodegenerative Diseases (DZNE). We told him about his scientific discoveries – and possible screening tests, vaccines and drugs for Alzheimer's disease.

They have been working as researchers on Alzheimer's for over 30 years. What were your most important scientific discoveries during this period?

Teacher. Dr. Christian Haass: I experienced the first great moment of my life as a researcher in 1992. We completely disrupted the field of research on Alzheimer's disease, which gave rise to a new beginning.

You must explain this in more detail.

Haass: Among the most notable changes in the brains of patients with Alzheimer's disease are the clustered protein deposits called amyloid plaques. It has long been thought that amyloid disease appears for the first time. But it was wrong. Everyone produces amyloid – from birth.

How did you discover it?

Haass: With a very simple trick: how did human kidney cells radiolabel and thus prove that these cells naturally produce amyloid in a natural way? This idea became the main title of the scientific journal Nature shortly after.

How did you learn to use kidney cells? After all, Alzheimer's disease is not a kidney disease.

Haass: We currently had these cells in the lab – in principle, it could have been other cells. After the discovery of amyloid, even in healthy people, the second important scientific finding is that brain immune cells are not sufficiently activated in the early stages of Alzheimer's disease – so you have to stimulate them rather than calm them down. The third finding relates to an enzyme related to amyloid formation – this enzyme works in principle as a paper scissors. But it was extremely complicated and it took years to fully understand how this enzyme works.

So, your entire research career revolves around this amyloid protein. According to your findings, have you developed the hypothesis of the amyloid cascade? What's up with that?

Haass: At the top of the waterfall is the amyloid, it is the cause of the disease, there is nothing that can shake it – regardless of whether healthy people produce the disease. 39; amyloid. But in patients with Alzheimer's disease, in simple terms, amyloid forms these plaques, these clots. It sets in motion a reaction chain that ultimately leads to the death of brain cells. An important point is that once the amyloid has triggered the disease, everything else is likely to follow independently of the amyloid. Then, for example, so-called TAU proteins propagate, that is, other deposits on nerve cells. Although amyloid is therefore the trigger of the disease, but not the only cause.

Why did not earlier Alzheimer's drugs have the desired results?

Haass: The big problem with all treatments is that they are late, no matter what medication you are taking. When patients come to the clinic, the brain is already partially destroyed, irreparably. In addition, the amyloid cascade has been going on for a long time and is already functioning independently of its trigger, the amyloid. We arrive too late, much too late, I am talking about 20 to 30 years.

So, you would need a screening test?

Haass: That's right, it's missing now. However, it should be done very early, at a time when patients are still completely free of symptoms. There is already a very good test, which was developed at the Tübingen DZNE – but it simply indicates the moment when the destruction of the brain takes place. It's too late, but this test is excellent for tracking the progression of nerve cell death or its prevention.

Are there realistic approaches for effective treatment of Alzheimer's disease?

Haass: I would say this: there are already useful drugs, but you should all test again – but early enough. We now know that clinical trials of genetically deficient patients will contract the disease 100% and when. These patients will be treated as soon as possible, that is to say from 18 years old. We should have started much earlier, because we can know how the disease works and how to prevent it.

This is only possible in patients who are still in perfect health. I do not think we need 5,000 new drugs, but we should test the ones we already have well and soon enough – they are not as bad as they are often.

How long will it take for an early mass detection test to be put on the market?

Haass: Unfortunately, this is not predictable.

And what about the development of vaccines?

Haass: In principle, vaccines already exist and, in my opinion, they have at least dramatic effects. They can prevent plaque formation and reduce existing plates. Unfortunately, they also have the disadvantage of not having yet managed to stabilize the memory – because the vaccine is too late, while the amyloid cascade is already started.

What are you looking for now?

Haass: To the immune cells of the brain. In 2013, genetic alterations were discovered that could significantly increase the risk of Alzheimer's disease. These genes were exclusively expressed in the immune cells of the brain. That made me think, because it can not be a coincidence if you can reduce all risk factors to one type of cell. So I started working on it with a very small team, with a technical assistant and a postdoc. Today, virtually all my lab employees work there.

With what results?

Haass: In simple terms, it's about activating immune cells to prevent the onset of the disease. We are already relatively far away, but there is also a lot of competition. Almost all major pharmaceutical companies are doing research on Alzheimer's disease and I have already received many requests for cooperation.

What do you think of Alzheimer's disease prevention tips: adequate sleep, no overweight, good nutrition, lots of exercise, low alcohol, non-smoker?

Haass: These are the usual truisms known for many years. Of course, there are risk factors such as obesity, high blood pressure, diabetes. And of course, we should stay active physically and mentally. This can easily influence the disease. But you can not stop them or heal them with so much sport and sudoku.

Are you afraid of becoming a day of Alzheimer's disease?

Haass: Yes of course. But I repress this: for example, I never looked at my own risk profile.

Why not

Haass: Because every time I forget something, I always think: Oh, now the disease has erupted.

What do you want as an Alzheimer's researcher?

Haass: That they give us more time and less public pressure. Alzheimer 's disease is a global problem and we need to work together on a global scale. There are problems that we can not solve alone. This applies to both global warming and dementia.

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