Translator: Gabriella Patricola Reviewer: David DeRuwe
AD.
Alzheimer's disease.
Each time I give this diagnosis to one of my patients,
I feel like I'm giving them a death sentence.
I'm sorry Sir, you will progressively forget ...
everything.
Everything you do, everything you've done.
All the ones you've loved,
and this is horrible.
But what is Alzheimer's disease exactly?
How does it start?
By forgetting your keys?
By not remembering the name of the previous speaker?
Or not knowing tomorrow that you've come here today
to this wonderful TEDx event?
As a doctor, I would say this is the most serious.
Alzheimer's disease is characterized by an episodic memory loss.
Forgetting the episodes of your life,
the recent events you just lived.
But you can forget
for many other reasons than Alzheimer's.
So it's not only a memory loss.
Alzheimer's is a brain disease,
but the thing is, that until very recently,
we could not see this disease in the brain during life,
and
new imaging techniques now allow seeing Alzheimer's lesions in vivo.
And this brings a lot of hope
to find a cure for this terrible affection.
So hoping to find a cure,
three years ago, I quit my doctor's job,
and I went to Harvard University
to do research.
So, instead of giving diagnoses
like a judge gives sentences,
I became a scientist
looking for answers,
kind of a detective.
And that is the adventure
I'd like to take you on today
because now is the time for even more research.
But let me start by giving you some background about Alzheimer's disease.
Here is the very first patient diagnosed by Doctor Alzheimer
with what he called at the time,
the dementia of forgetfulness.
Dementia comes from Latin.
de mentia, literally, losing your mind.
Losing what makes you human.
A lot of diseases can cause dementia.
A brain tumor, for instance.
Alzheimer's starts with forgetfulness
and memory loss
that progressively evolves
to dementia,
a stage at which you are no longer able
to care for yourself.
That is the stage everybody is afraid of.
And we have very good reasons
to be afraid.
No treatment, and it seems unavoidable.
The two main risks for Alzheimer's are age and genetics.
Sorry Madam, I can't change your genes.
And whatever we do, we're all getting older.
This just seems hopeless.
But still, why not trying research.
Maybe if we understand better what's happening in the brain,
we can fix it.
Like Hercule Poirot would elucidate a murder in Agatha Christie,
let's try to understand how, why, and when Alzheimer's kills our mind.
But above of all, what could we do to prevent this murder?
Doctor Alzheimer paved the way
by giving a description of the brain pathology.
After his first patient died, he performed a brain autopsy
and identified two lesions
which, together, define Alzheimer's disease.
These two lesions
are amyloid plaques and tau tangles.
Sounds complicated, but this tau, after the Greek letter with that name,
and amyloid, are still, today, a century later,
the two main suspects
in Alzheimer's disease.
But if a doctor can't see them,
he can never be sure someone has Alzheimer's.
Early detection and prevention
are impossible then.
However, we learned a lot from these autopsy studies.
And the most important thing we have learned
is that amyloid plaques are not only present
in the brain of patients with Alzheimer's dementia,
but also in normal individuals,
like you and me.
And the older we get, the more common it becomes.
At the age of 35 years old,
a third of us
have amyloid pathology in our brain.
But, wait a minute.
Should we care about this?
Is that Alzheimer's disease,
having amyloid in the brain but a normal memory?
I think we should care about this
because if we look at the risk for Alzheimer's dementia,
we see a similar curve, 15 years later,
at the age of 90 years old.
It is a third of us
who will suffer from Alzheimer's dementia.
We should try to do something about this.
And I think these 15 years,
during which pathology slowly builds up,
but memory symptoms are not present yet,
are a wonderful opportunity
for who wants to prevent the disease
from occurring.
Catching the killer, before the murder is committed.
Brain autopsy.
That's quite a late stage for doing this.
So the first breakthrough I'd like to mention to you,
is amyloid imaging.
For the past 10 years now,
we've been able to perform a scan
and visualize amyloid in the brain
during life, in red on this scan.
And we could confirm that at the age of 75,
a third of us
have a positive scan for amyloid.
The big lesson here is that this complicated thing
named amyloid
is not important for memory right now.
But it has a drastic impact
on how memory will evolve in the future.
So, what's happening?
How can someone have a head full of amyloid,
his memory is working fine,
and then suddenly he becomes demented?
What's new?
I think that the second lesion in Alzheimer's
has now come into play:
tau pathology.
So tau pathology
is strongly correlated with memory.
In individuals who had a normal memory during life,
only few tau pathologies observed at autopsy,
what you can see here, on the left, in brown.
But for individuals who had mild cognitive impairment
at the end of their life,
we observed more tau pathology.
And an expanded tau pathology all over the brain
is almost always associated with dementia.
So amyloid might be the first culprit in Alzheimer's disease,
but tau seems closer to the symptoms.
Tau pathology starts accumulating in the brain region
that is the most important for memory,
and the more it accumulates, the more memory declines.
So let me share to you my current understanding
of Alzheimer's disease
and compare this to the three steps of a murder.
First, someone wishes you dead.
And actually that might happen more often than you think.
But it doesn't necessarily mean
you will die.
This is amyloid
building up in the brain.
That is actually quite frequent with age.
It doesn't necessarily mean you will have dementia.
But for sure that increase the risk.
If you have no amyloid, no Alzheimer's.
If no one wishes you dead, you won't die from a murder.
But in the second step, the one who wishes you dead
actually contacts a killer.
And that's where it becomes more serious
because he asks him to prepare the murder,
and that is amyloid increasing tau pathology.
No memory symptoms yet,
but soon the patient will come and see his doctor
because he has noticed some memory loss.
And bam! He receives a death sentence.
He learns he has Alzheimer's disease.
And very little can be done to save him.
Many brain regions have been destroyed
by amyloid and tau,
and repairing the brain
would be as difficult as resuscitating someone
after a murder.
What we should do is prevention.
Preventing amyloid and tau from destroying the brain,
but that was not quite possible
if we could not see these lesions
during life,
and it is only three years ago
that tau scans were developed in Harvard University.
And this invention, tau scans,
is probably a turning point in Alzheimer's research.
Because now we have the technical capability
of observing both amyloid and tau
because now we have the two main suspects in custody,
and we can question them.
So I went to Harvard to learn more about it.
And the first tau scans
confirmed what we knew from autopsy:
tau is really bad for your memory.
If you have a lot of tau pathology in your brain,
you're probably going to be demented.
In contrast, amyloid increase very early,
at the time where our memory is still normal,
and it can stay normal for many years, despite amyloid,
and that is the point we should try
to prevent Alzheimer's.
Over the past 20 years,
95% of clinical trials in Alzheimer's disease
have failed.
But we were looking in the dark.
We could not verify in humans if a drug was effective or not.
Except in a very long trial, we were waiting for cognitive decline.
Basically we needed the murder to happen to identify the murderer.
No prevention was possible.
But now that both amyloid and tau scans have been developed,
we can start thinking of prevention therapies.
So now that we understand
a little bit better how this plot is built,
now that we understand better Alzheimer's disease,
let's imagine strategies to fix it.
Who do you want to see in jail?
The one who wished you dead or the killer?
I would say both of them.
But actually stopping one might be enough to prevent the murder.
So far many clinical trials have intended to remove amyloid from the brain,
and they were not quite successful.
But one of the potential reasons
is that these trials included patients with dementia,
a stage that might be too late to be effective.
So currently, a very large American trial
is giving anti-amyloid drug to normal individuals
who are older than 65
and have evidence of amyloid on a scan.
And we should have the results of this very first preventive trial
in three years from now.
But we should probably also follow other tracks,
like drugs against tau pathology.
Stopping the killer
might be the most effective way to stay alive.
And to share a personal conviction,
I think we're still missing a very important piece
in Alzheimer's disease.
Who is the messenger?
How do amyloid and tau interact?
Actually, no one really knows.
But now we have the tools to investigate these questions.
We can look for answers.
And that is a game changer.
The research we will conduct today
will help us not only to live longer,
but also in a better mental health.
However, we need to hurry if we want to catch these criminals,
if we want to avoid the serial killing predicted by global aging.
If we do nothing,
we all are going to have Alzheimer's
once we've been cured from cardiovascular disease
and cancer.
So let's stand together in this fight
and make aging fun again.
This detective story can have a happy ending.
Over the past few months,
I resumed a memory clinic, every Wednesday in Brussels,
and I'm still doing research.
But now, with this increased knowledge, I can reassure my patients
and their families
they're not crazy.
Their memory symptoms have a biological explanation,
and you also know why now.
And we can do more research to understand this better
and try to fix it.
And this hope is really important
for the patients with the disease,
but also, for you and me,
who might have the disease in the future.
My deepest wish
is to see a prevention for Alzheimer's disease
as soon as possible.
And if we all fight for this,
I am sure we can do it.
Thank you for supporting research.
(Applause)