Translator: Claudia Sander
Reviewer: Queenie Lee I'm working on brain killers. Brain killers? Yes. Alzheimer's, Parkinson's,
Huntington's, prion diseases, frontotemporal dementia. They're also called age-related
neurodegenerative diseases because our chances to get one of these
increases as we get older. Ten percent of people aged 65 or more
do have a neurodegenerative disease, and there are no cures for them. Current treatment, if available at all, only alleviates symptoms
and for a limited period of time. 30 million people in the world
have Alzheimer's disease, and about five times less
have Parkinson's disease. The number of people
with Alzheimer's disease will increase to
about 100 million in 2050. Why such a stunning increase? Well, we get older, and our life expectancies will continue
to increase in coming years. That's awesome, isn't it? But the question
we have to ask ourselves is, "Does it make sense if we're not able
to keep our brains working properly during all these extra years?" By the way, the cost of care
for Alzheimer's disease patients will become unaffordable. From a cost of currently
200 billion dollars per year, for the American society, it will increase to 1.2 trillion in 2050. We have to stop this new epidemic. One of my best friends, Zack,
told me his story. He had an uncle called Bob. He loved him. Bob had been a nurse
in a surgery department for all his life. He never married. He was always secretly in love with one or another of his female
colleagues in the department. He was so smart. He was the most resourceful
person on Zack's planet. He knew how to deal with injuries,
those of the body and those of the mind. But Uncle Bob's greatest attribute
was his sense of humor. By the way, he always knew how long
it would take for a patient to recover. He had his own criteria
and he was rarely wrong. Zack cherished to go
for bicycle rides with his uncle. Sometimes they would get lost. So Uncle Bob would stop, sit up straight
on his bicycle and emit a loud "Darn!", which was the highlight of the ride. (Laughter) They would eventually find a way home, it didn't matter
how long it would take them. After a long winter,
where Zack had been very busy traveling, Uncle Bob went for
a bicycle ride on his own, but this time he didn't return. A good man found him
sitting next to his bicycle and brought him back. This was the beginning
of a long downhill road from which there was no return. Uncle Bob kept his humorous demeanor
for quite a while, letting go a "Darn!"
when he didn't remember what his nephew had told him one hour ago or when he was unable to learn a new game. He self-diagnosed
with Alzheimer's disease, but he didn't try to guess
how long it would take him to recover. Rightly so. He progressively forgot everything, from how to use the water faucet
to who Zack was. But what he kept for the longest was his love for this man
who pretended he was his nephew. After six years, Uncle Bob left for a place
where bicycles are no longer needed. I'm a scientist. The reason why I'm talking to you today is because something
very important is changing. 15 years ago scientists were still arguing
about which protein is responsible for the mess in the brain
of a person who has Alzheimer's disease. But after years of lab work
around the world, of testing new hypotheses
with newer methods, of developing new experimental models, the puzzle of the disease process
finally assembles. In our brains, we have
cells called neurons. Neurons are born to communicate, so they have long extensions that convey information
from one neuron to another by electrical and chemical signals. They also have a cell body
that contains their genetic code and most of their little factories
to produce energy and proteins. Proteins are very important
molecules in our bodies. They have many functions, such as maintaining a scaffold, transporting one molecule
from one place to another, facilitating chemical reactions,
or even cutting something. They're then called enzymes. Now I want to show you what's happening
with one particular protein which is present inside
and at the surface of neurons. Let's pretend for a minute
that this flower is this protein. It's called the amyloid precursor protein, or APP. APP is a useful protein,
it helps neurons when they grow. But it has one major problem: it has a very dangerous part
that has many thorns, that goes, let's say, from here to there. When everything's fine, like in the brain
of a young and healthy person, APP gets cut in the middle
of its dangerous part, releasing two harmless fragments. But in the brain of a person
who has Alzheimer's disease, two other enzymes become more active, and they cut APP
at the top of the dangerous part, and at the bottom, like this, releasing, as you can see, intact this dangerous part,
which is called the Abeta fragment. This wouldn't be a problem if it happened to only one APP molecule. But the problem is it happens
to many APP molecules. And the obsession
of Abeta fragments is to aggregate, which means that they
group together, like this, and form thorny bundles
aggressing the neuron. This is one example of a protein
involved in Alzheimer's disease. There are other proteins
that are involved. Some are even involved
in several diseases, such as, for example, the prion protein, which is the primary player
in prion diseases, such as mad cow disease,
or Creutzfeldt-Jakob disease, or a protein named tau, which is also involved
in frontotemporal dementia. The protein tau, for example,
stabilizes tube-like structures that are necessary
for maintaining the neuron's shape and transporting little vesicles
containing useful molecules to its extremities. In Alzheimer's disease,
the tau protein gets modified, aggregates like Abeta did, detaches from the tube-like structures
which damage the neuron. Of course, there are still
many missing pieces in the puzzle, gaps in knowledge that scientists
continue to work on, and it's extremely important to continue
this basic research to advance knowledge. But we already have
a roadmap of what's happening. And this roadmap indicates several
critical steps in the disease process, several proteins or pathways, that will serve as targets
for therapeutic agents. In other words, we have a handle on how to develop
disease-modifying treatments. So, now, what about the other diseases? Parkinson's, Huntington's, prion diseases? I don't have the time
to specifically explain what's going wrong
in the brains of these patients. But the bottom line is that these diseases
are also caused by specific proteins that misbehave and aggregate, and that we have identified a number
of critical steps in the disease processes to allow for the development
of disease-modifying therapies. Now, this was all about
the progress we've made in understanding these diseases. But, at the same time, huge advances have been made
in the field of drug discovery. We know better how to block
a specific protein or even reduce its amount. We can screen hundreds of thousands
of molecules per day in the search for those
exhibiting the desired property. And chemists are inventing continuously
new methods to modify molecules and make them better drugs. Plus, we have made leaps in the field
of regenerative medicine and stem cells. Do you know, for example, that it is possible
to take a cell from the skin and transform it into a neuron? So here's an idea worth spreading: it's no longer time to just hope for cures
of neurodegenerative diseases; it's time to hurry on the road that has unfolded and continues
to unfold in front of us. Scientists know what to do
to develop these cures, but they need your support. Anyone of us has the power to influence where our society,
where our world, is headed. Take the time to think
where you want us to go. And you might already know
what you can do to help. Or you might discover it later. But, in any case, if all of us think that it is
a worthwhile cause preventing 100 million people from getting
Alzheimer's disease by the year 2050, then Zack will never have to worry about not finding his way back home
from a bicycle ride. (Applause)
