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Biologist Bart De Strooper, one of the world's leading experts on dementia, makes a gloomy prognosis.
If humanity does not achieve an effective treatment against Alzheimer's soon, very soon, the future will be catastrophic.
An international consortium has estimated that the number of people with dementia will triple in the next quarter century, exceeding 150 million.
“Who will take care of them?” asks De Strooper, born in the Belgian town of Tielt 64 years ago.
The German psychiatrist Alois Alzheimer described the first case of the disease that bears his name in 1906. More than a century later, the scientific community still does not understand the exact mechanisms of dementia.
Almost three decades ago, De Strooper discovered a kind of molecular scissors that gives rise to amyloid, the protein substance that accumulates in the brain and has historically been accused of causing Alzheimer's.
The Belgian scientist, from the Center for Research on the Brain and its Diseases in Leuven, defends that amyloid is rather a trigger, causing an inflammatory reaction in brain cells.
Once started, this reaction is unstoppable, which is why the new drugs that eliminate amyloid fail to prevent dementia, according to the biologist.
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A mouse with 100,000 human neurons in its brain illuminates the enigma of Alzheimer's
De Strooper's laboratory has just created mice with 100,000 human neurons embedded in their brains, in order to illuminate the enigmas of the disease.
At 64 years old, the researcher races 15 kilometers, but he emphasizes that sport is not miraculous: two out of every three cases of Alzheimer's depend on the genetic lottery, he explains during a visit to Madrid to participate in a conference organized by the Ramón Areces Foundation and the Springer Nature publishing house.
Ask.
Obviously your mice with 100,000 human neurons will not have human gaze.
Answer.
Not at all.
People fantasize, but these mice basically look normal.
A human brain has about 100 billion neurons, so 100,000 cells don't make anything even close.
Q.
But a mouse only has 70 million neurons in its brain.
There, 100,000 human neurons are already something.
A.
Yes, but let's think about a country of 70 million people and a small city of 100,000 inhabitants.
It doesn't have a big impact.
Some integrate into the brain, but simply act like mouse neurons.
Other human neurons form a small cluster, somewhat isolated from the rest of the brain.
It is as if you prepare a network of computers and they are all from Apple, but you add another from Hewlett Packard in the middle.
The result will be the same, it is nothing spectacular.
But the science we can do is spectacular, because in these mice we create amyloid plaques, as in Alzheimer's.
Mouse neurons do not react much, but human neurons develop all the pathology of Alzheimer's until they die.
It is a fantastic model.
The problem is that the brain of a mouse is like this [makes the gesture of picking up a pea with two fingers] and that of a human is like this [uses both hands to lift an imaginary brain].
It is not a perfect model, of course.
The cancer field is decades ahead of us, because it receives much more funding.
They have specific drugs against this necroptosis [cell death with inflammation] and we are testing them in our mice.
Q.
Do they work?
A.
We will know in a year.
We have to wait and then we will open his brain.
If they work, they will probably lead to an oral treatment, a pill.
It's important for people to realize the complexity: we have drugs to eliminate amyloid and then we have another drug with the potential to protect neurons that are dying.
The big question is: Will it be enough?
We have a preliminary study that shows a slight effect on maintaining memory in these mice.
It's not spectacular, but a slight effect is good news.
The regulation for experimenting with mice is ridiculous, we should reflect
Q.
Do you think human neurons should be introduced into monkeys?
A.
Good question.
When we talk about animal experimentation, it seems as if all animals were the same and we didn't care about them.
Mice already have strict regulation, which is ridiculous when you put it into perspective.
If a restaurant has mice in the basement, they kill them and no one cares.
On the other hand, when we do an experiment with a mouse, minimizing suffering, we have to do a lot of paperwork.
We should reflect on this regulation.
Monkeys are closer to humans and I think the legislation should be more rigorous.
Nowadays I think I can solve most of my questions with this humanized mouse, so I'm not going to use monkeys.
But in other types of experiments we will need to use monkeys.
If it is not in Europe, it will have to be outside Europe.
Q.
What kind of experiments?
A.
Well, we have developed an antisense oligonucleotide [a kind of genetic
band-aid
] to treat a specific Alzheimer's mutation.
It works in patient cells in the laboratory and we have indications that it works in our mouse.
But we cannot inject these oligonucleotides into a human without an intermediate test in monkeys.
Q.
Will they have to do it in China?
A.
There are still experiments with monkeys in Europe, so I hope we can do them here.
That is the dilemma.
If you do them in Europe, you determine the conditions.
However, if you ban them here, they will still be made in China, Japan or the United States, and you will no longer have a say in the matter.
And if they find a drug against Alzheimer's in the United States or China, thanks to experiments on animals that you have banned, what hypocrisy would it be to allow those drugs to reach Europe to treat our Alzheimer's patients!
The animalists' argument is that we no longer need animal experiments.
There is nothing further from the truth.
One day I spoke on the radio and received a wave of hate on social media, they told me that what I was doing was totally immoral and that I should carry out the experiments with my children.
I wonder what they do when a restaurant owner kills a mouse.
They were completely out of character attacks.
The day may come when it will be possible to perform neuron transplants in people with dementia
Q.
Surely there will already be scientists in China thinking about putting human neurons in the brain of a monkey.
A.
Maybe, but it's not that easy.
And we also inject human neurons into mice to bring them closer to humans.
The monkey brain is already much more similar to the human one, I see no reason to humanize it, taking into account the difficulties.
I do not think they do.
We do these experiments to understand the disease.
And they have already changed my way of thinking.
The day may come when it will be possible to perform neuron transplants in people with dementia.
Once you have dementia, it's too late to cure your neurons, but if you can replace some of the missing ones, you might be able to restore your cognitive abilities.
That's what we've seen in mice.
Q.
A transplant of neurons from another person?
A.
No, from yourself.
You take skin or blood cells, generate stem cells from them [capable of becoming any type of cell in the body], induce them to be precursors of neurons and transplant them to the brain.
There they grow, make connections and restore circuits and thinking.
That's the theory.
In Parkinson's there are already clinical experiments underway: transplants of neurons in the substantia nigra [a region of the brain stem implicated in Parkinson's].
I never thought it would be possible in Alzheimer's, because it is a diffuse disease, while Parkinson's has a very specific goal to restore.
However, it has now been shown that these neurons can be integrated into brain circuitry, especially with the experiments of my colleague Pierre Vanderhaeghen.
Theoretically it is possible to treat patients with their own neurons.
You could transplant your own neurons into your brain.
Q.
The technical name of your animals is human-mouse chimera.
Chimeras were monsters from mythology.
What would you say to people who think you are creating monsters?
A.
I would ask you to observe what we do.
This is not
Frankenstein
, we are simply trying to understand the disease, not create better or different things.
It's about understanding how human neurons get sick and seeing what we can do to prevent it.
If you want to say this is a monster, that's your way of thinking.
I do not force you to do the experiments and I do not force you to take any medication that may arise from this research.
This is not 'Frankenstein', we are simply trying to understand the disease
Q.
You are 64 years old.
Do you think you will live to see an effective treatment for Alzheimer's?
A.
Without a doubt.
We already have the first effective treatments authorized in the United States, but I don't know if they will be approved in Europe, because they are quite expensive and the results are not magical.
Q.
Are you referring to lecanemab [a treatment from the Japanese pharmaceutical company Eisai and the American company Biogen, which eliminates amyloid and delays cognitive decline by 27%]?
A.
Yes, to lecanemab and donanemab [another similar treatment, from the American pharmaceutical company Lilly, which delays cognitive deterioration by 35%], which will be authorized soon.
Q.
And what do you think of aducanumab [the first treatment against amyloid, from Biogen, approved with controversy in the United States in 2021]?
A.
Aducanumab has now been abandoned.
The clinical trial was done very poorly, its results were not convincing and they have never gotten rid of that stigma.
They used pressure groups to get the treatment approved.
They also made many other mistakes.
I think they were very arrogant to ask for up to $50,000 for each treatment.
The other two drugs do have an impeccable record.
There are side effects, but they are known risks.
The results are not spectacular either, but what do you want with the first drug?
I was a doctor in Paris when AIDS appeared and no one knew what to do.
The first pills arrived and you had to take them four times a day to gain a week of life.
Two decades later, AIDS has basically been cured.
These first Alzheimer's drugs are the beginning of a new era.
And we need more incentives to find cheaper drugs that lower amyloid, even if we don't immediately see the slowing of dementia.
You have to give a carrot to the industry, because an investment of billions is needed to obtain a drug like this.
We need governments to promise that if a drug like this is available, they will approve it.
That will speed up the investigation tremendously.
Q.
Are you scared by the idea of suffering from Alzheimer's?
A.
Yes, it scares me.
My mother died from Alzheimer's.
The idea of suffering from Alzheimer's scares me.
Q.
What if in the next 30 years we don't discover an effective treatment?
A.
It will be a disaster.
Q.
It is estimated that there will be 150 million people living with dementia in 2050, almost triple the number now.
A.
It is a disaster worldwide, but let's look at our countries: Spain, Belgium, England, France.
They have a very good health system and an aging population.
Who is going to take care of all these people?
We already need to take the best nurses and caregivers from poor countries to care for our aging population.
Multiply this by three.
I can only speak in terms of disaster if we don't get some treatment.
I am 64 years old and I still run 15 kilometers.
Prevention is very important to avoid dementia in general, but not so much for Alzheimer's.
We'll need a treatment, something you can take when you're 60 that eliminates the amyloid, to postpone the disease for five or six years, which would be perfect.
Otherwise, I don't see how we will move forward as a society.
Q.
Is Alzheimer's research underfunded?
A.
It receives extremely little funding.
In Europe it is a disaster.
I will never say that cancer should receive less money, I think it gets what it needs.
What I'm saying is that dementia should receive the same.
Q.
What is the difference between Alzheimer's funding and cancer funding?
A.
Cancer receives 15 times more, in money and everything.
There are about 55 million people with cancer in the world.
And there are about 58 million with dementia.
It is a problem of the same magnitude, but in the databases there are four and a half million studies on cancer and barely 350,000 on neurodegeneration.
About 15 times more.
Alzheimer's research receives extremely little funding, 15 times less than cancer
Q.
A Spanish scientist, Pío del Río Hortega, discovered microglia [cells of the nervous system that defend it from attacks] in 1919.
A.
He is our Pope.
Q.
What is the role of microglia in Alzheimer's?
A.
It is crucial.
Amyloid is a trigger, but then there is the reaction of microglia and other cell types.
Microglia see amyloid as a kind of infectious agent and fight against it.
By doing so, there is inflammation, which is not very healthy for the brain.
Microglia send signals to other cells: “Come and help me!”
Thus a chronic cellular reaction arises that, in my opinion, is initiated by microglia.
He is the main actor.
A large part of my research now focuses on microglia.
I believe that we will discover drugs capable of attenuating this inflammation.
Q.
A Spanish scientist claims that thinking that amyloid is responsible for Alzheimer's is like arriving at a crime scene and believing that blood committed the murder.
What does he think?
A.
Maybe it was logical 10 or 15 years ago.
I understand why you say that, but it doesn't take genetics into account.
There is absolutely clear evidence that if you have a problem with amyloid, you can die.
It's like arriving at a crime scene, seeing a gun, and coming to the conclusion that that gun is probably the cause.
Q.
Is amyloid the gun?
A.
Amyloid is the gun, yes.
But it is more complex than a gun, because with a gun you shoot and the patient is dead.
In real life, the amyloid is there and then there is a reaction, an inflammation.
We need to avoid simplisms.
It is a chronic disease, like cancer.
The body, in youth, is able to maintain amyloid at healthy levels.
In old age, our resistance decreases and this becomes a problem.
It is a very slow disease.
A study by the Alzheimer's Association of the United States showed that, if we find a drug capable of delaying the onset of dementia for five years, the number of people affected will remain at the current numbers.
We could stabilize the problem, which would be great.
I am optimistic.
That is our first objective: to delay the disease for five years.
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