Detect and prevent Alzheimer’s disease before memory loss | Bernard Hanseeuw | TEDxUCLouvain

After 65 years old, one out of 10 have Alzheimer’s disease …
Even worse, one out of three have the hallmark brain lesions of Alzheimer’s. Worrisome? Indeed. However, having lesions 10 to 20 years before symptom onset is a wonderful opportunity for whoever wants to detect this terrible affection. Since 2013, the hallmark pathologies of Alzheimer’s can be detected using a PET scan. New research avenues are thus opening, and with them, the hope of developing preventive therapies.

Dr. Bernard Hanseeuw graduated as a medical doctor at UCLouvain in 2007. Four years later, he defended a PhD thesis on brain imaging in early Alzheimer’s detection. After his residency in neurology, he left for Massachusetts General Hospital/Harvard Medical School to train in molecular PET imaging of amyloid and tau proteins. Bernard Hanseeuw conducts research in Boston and Brussels; he aims at better understanding the pathophysiological mechanisms leading to Alzheimer’s pathology in older adults, to guide clinical trials to success.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at https://www.ted.com/tedx

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)