Nova (1974–…): Season 43, Episode 10 - Can Alzheimer's Be Stopped? - full transcript

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The memory lapses
were troubling:

forgotten appointments,

misplaced objects,
irretrievable names.

Reporter Greg O'Brien
dismissed them

as the result of too much stress
and normal aging.

I was experiencing horrific
short term memory loss.

I wasn't recognizing people
that I knew.

I wasn't recognizing places.

And I just felt if I ignored it,
it would go away.

Then a bike crash resulting
in a concussion and brain scans



unmasked the problem.

Alzheimer's, a progressive,
incurable brain disease,

and the most common type
of dementia.

Greg was not just losing
his keys, but also his memory.

At age 64, he's chronicling
the progression of his disease.

One of his first priorities

is to shatter the stereotype
of Alzheimer's.

Alzheimer's is not just
your grandfather's disease.

There are scores and scores
of people

who are in the early stages
of Alzheimer's right now

and may not even know it,
because this is a disease

that can take 20 years or more
to run its course.

Tell me how many
children you have.

I'm sorry, I'm...



It's just not there?

It's just not coming up.

What is the date today?

I don't know.

Where are you originally from?

I think...
that's a toughie.

Alzheimer's is not only my
story, it could be your story,

or the story of a relative
or a close friend.

What's this?

That is a, um...

The human toll is staggering.

It starts with a "B."

Over 40 million people
are afflicted with Alzheimer's,

including five million
Americans.

And the numbers are rising.

How about this thing,
what's that?

Baby boomers are coming up fast,

and it's estimated that
10,000 individuals in the U.S.

turn age 65 every single day.

And age 65 is where
it really ramps up quickly

the likelihood of developing
Alzheimer's disease.

So we're projecting that
it's gonna be ten million

in another 20 years.

It's going to grow
to epidemic proportions.

It has the potential
for bankrupting

the entire medical system.

But I also have to think
of the human side of this.

It's hard to think of anything
that's more sad

than a person who's done
so much in their life

and accumulated
a lifetime of memories

and to have all of that lost
in the their last few years.

Oh, that's my youngest daughter.

No...

And the inability
to form new memories

and remember things that are
happening to them every day

gets lost progressively
in Alzheimer's disease.

And as you can imagine,
that's terrifying.

The urgent need to find
a treatment for Alzheimer's

is driving a global race.

Virtually every large drug maker
is competing.

One place where the stakes
are high is at Genentech,

a biotech company
in South San Francisco.

Like many of its rivals,

Genentech is developing
a treatment

to prevent or slow Alzheimer's.

But it faces stiff competition,

with some 20 drugs in trials
in the U.S. alone.

The probability of failure
is high.

Less than one percent
of Alzheimer's drugs tested

have been approved,

and none of them
can stop the disease.

Medical director Carole Ho
believes that's about to change.

15 years ago,

when I was starting
to study Alzheimer's Disease,

I did not think that
in my lifetime

I would ever see a therapy that
would really benefit patients.

Given the acceleration over
the last ten to 15 years

in understanding the disease,

and now having very targeted
therapies that go directly after

what we think the source
of the disease is,

I'm incredibly hopeful.

Neurobiologist Ryan Watts
agrees.

I think we know so much
that it's a great place

to really put in
the intellectual power

to try to figure out
how to treat this disease.

"Cure" is always a strong word,
but I think

what I imagine is that
we develop a treatment

that can then become
a prevention.

The search for a treatment
is decades old,

the progress slow
and incremental.

I know that a lot of people
wonder,

"How have you gone

"through 25 years without
having a medication

successfully make it
to the marketplace?"

And I think the only
real answer to that is

we were learning
every step along the way.

The disease was first
identified in 1906

by psychiatrist Alois Alzheimer.

During an autopsy, he examined
the brain of Auguste Deter,

who had entered
his mental hospital

delusional and confused.

Before her death, she told him,
"I have lost myself."

Alzheimer rejected the notion
of madness,

suspecting a physical illness
had killed her.

A sliver of stained tissue
magnified hundreds of times

proved he was right.

I think it was very striking,
what he must have seen,

looking at these big clumps
of protein, known as plaques.

In fact, they were everywhere,
riddling the brain.

He also observed tangles,
which you can see here,

inside the neurons.

Alzheimer sketched the features

of the disease
that would bear his name.

Plaques and tangles

clearly distinguished it
from other dementias.

But were they a direct cause
of the disease?

To find the answers, scientists
searched for rare families

where Alzheimer's was passed
from generation to generation.

Pa, pa.

On the outskirts
of Medellín, Colombia,

Ramiro tends to his father
Nelson.

For eight years,
he has been sick with dementia

and unable to work as a driver.

Six months ago,
he was able to walk.

Slowly, but he could stand
on his own.

Now he no longer recognizes me.

He doesn't know my name.

He doesn't speak.

He doesn't understand anything.

He's a total infant.

Nelson is part of a family

where dementia starts unusually
early, around age 45.

Dr. Francisco Lopera,
a Medellín neurologist,

has treated the family
for decades,

starting with Nelson's mother.

What I found most
shocking was her age...

that she was a young person
with Alzheimer's-type dementia.

I was also struck by the fact
that several of her relatives

had the same history of disease.

From the time we identified
the first family,

we knew we were facing something
very important.

Lopera would soon discover
other families

with the same pattern
of illness.

In a nearby town, Salome tends
to her aunt, Yolanda,

ill for over a decade.

Salome has watched dementia
tear apart her family.

I started to realize
that it was something

that went back
to my great-grandmother.

That's when I started
to get scared.

I realized my mother
could get sick.

In addition to worrying
about my mom,

I really worry that
I might get the disease.

That's why I don't want
to have children.

Lopera asked psychologist
Lucía Madrigal

to help him construct
genealogies of the families,

suspecting an inherited disease.

But the families had
their own explanation.

They believed
they had been cursed, charmed,

or given some kind
of magic potion.

And people make up stories

to explain and bring meaning
to what they're going through.

So they hung on
to this idea of witchcraft,

the myths and beliefs
of the region.

As Lopera followed a trail
of dementia across Colombia,

his work caught the attention
of Ken Kosik,

an Alzheimer's researcher.

From the moment I saw
this piece of paper

on which he had just mapped out
a small piece of this family,

it was clear it was genetic

because if they had
one parent affected,

they were facing a 50/50 chance
of either getting it

or not getting it
in these families.

And the families
were large enough to say that.

There wasn't just, like,
two people.

It was 15 people,

and you can see that
about half would get it.

That is a clear-cut signature
of a genetic condition.

Lopera was convinced
a rare form of dementia

determined by genes
plagued the region.

But were the afflicted
families related?

To find out,
he visited local parishes,

combing through birth, death,
and marriage records.

As he traced their ancestry,

an extended family
of 5,000 members emerged.

Those with dementia descended
from a Spanish conquistador.

To find out if their illness
was Alzheimer's disease,

Lopera examined the brain
of a victim.

When he compared it to a healthy
brain, it was abnormally small.

He sent it to Kosik.

And we went right into my lab,

cut the brain, stained it,
and were able to see that

the brain was absolutely full
of plaques and tangles...

the diagnostic signature
of Alzheimer's disease.

Lopera's team had found

the largest extended
Alzheimer's family in the world.

Clearly, there was
a genetic explanation.

But what gene was involved?

And did it implicate
either plaques or tangles

as the cause of Alzheimer's?

In the 1980s,
attention focused on plaques

after scientists discovered
they were made from a protein

called amyloid beta.

Little is known about its role
in the brain.

Normally, fragments of amyloid
are cleared away.

But in Alzheimer's,

they accumulate like garbage,
forming plaques.

Could a faulty gene
be the problem?

Everybody's got a copy
of the amyloid gene,

and that gene
gave us geneticists

something to work with,

something we could look
for mutations in.

John Hardy and Alison Goate

studied the gene
in British families

who, like the Colombians,
had a history of Alzheimer's.

Like all genes in our DNA,

the one responsible
for the amyloid protein

is made up of four
chemical bases

abbreviated by the letters
A, T, C and G.

Goate probed the gene
in afflicted families,

hunting for incorrect letters,
known as mutations.

This is detective work.

We were reading
the DNA sequence by hand

and looking for the one
spelling mistake

that was causing disease
in the families.

A, T, T, C, C...

Among the 3,000 letters
making up the gene,

Goate finally found a mutation.

In the DNA of one family,

everyone with Alzheimer's
had the same mistake:

a "C" replaced by a "T."

We could see,
looking across the gel,

"This one's affected,
yes, they carry the variant."

"This one's unaffected,
they don't carry it."

So we were pumped, I dare say.

We definitely found something.

You know, you're looking at it
and you're saying, "Wow!"

The mutation appeared to cause
amyloid to clump into plaques.

And we immediately realized

that amyloid was central
to the disease process,

and what researchers should do

is focus on reducing amyloid
in the brain.

Hardy and other scientists

amyloid plaques trigger
the cascade of destruction,

including tangles,
that causes Alzheimer's.

Soon, other mutations were found

that also implicated plaques.

The one afflicting
the Colombians

was pinpointed by Alison Goate,
working with Lopera's team.

Now, the families confronted
a stark reality:

anyone who had inherited
this mutation

was destined to get Alzheimer's.

There was no escape.

At first, it was very difficult
to tell them they had a disease.

It's real, and every child
has the same odds.

Suddenly, we were opening
Pandora's box.

I used to ask if we were doing
the right thing.

The box had been opened,
but where was the hope?

But on the horizon,
there was hope.

The knowledge gleaned
from these families

was pushing the field forward.

Drug makers now had a target,

and people at risk everywhere
stood to benefit.

After years of research,

Genentech,
like many of its rivals,

has developed a potential
Alzheimer's drug.

It's designed to target amyloid,
which makes up plaques.

You look at a human brain,

and they start to form
these little clumps,

or pieces of garbage.

We ask ourselves, number one,
how can we stop the production?

And number two,

how can we get rid of the
existing garbage that's there?

That's the problem,
and the solution arises

from the tools that we have
at hand,

which are basically the body's
own immune system.

The drug is an antibody,

similar to the ones found
in our blood.

It binds to amyloid

and signals immune cells
to destroy it.

Many companies are testing
similar antibodies,

and some have run
into serious problems.

Shehnaaz Suliman,
who helps manage the testing,

is well aware of the challenges.

We're all extremely hopeful,
but also extremely nervous

because the history
of Alzheimer's drug development

has been fraught with difficulty
and failure.

Some drugs have caused
brain swelling

in patients who have been
in clinical trials.

So that's a side effect that
we will track very closely.

The drug will be tested
in a series of clinical trials,

divided into three phases.

So we ran a relatively large
phase one clinical trial,

and that was designed to test
this question around safety.

And phase one indeed showed that

the drug is not going to cause
this swelling in the brain.

So that's a good start.

The drug was ready
for a phase two trial

to determine its effectiveness
and the best dose.

It would first be tested
in the U.S. and Europe,

not on the rare familial type
of Alzheimer's,

but on the most common form,
where the cause is less clear.

The vast majority of Alzheimer's
occurs after 60,

and, yes, there you see genes
playing a role.

But they don't guarantee
the disease.

Over 500 people sign up
for the 18-month study,

treating patients like Joanne

with mild to moderate
Alzheimer's disease.

Hi, Dr. Salloway.

How are you doing?

Good, how are you?

Stephen Salloway oversees
clinical trials

at Butler Hospital
in Providence, Rhode Islan

The early stages
of Alzheimer's disease

if you have a good,
stable living situation

can be associated with a very
good quality of life.

However, it's a progressive
illness,

and our goal for this trial
is to see if we can actually

slow the progression
of the disease process itself.

A third of the patients will get
a high dose of the drug,

a third will get a low dose,

and the rest will get
a harmless placebo.

The trial is
a double-blinded study,

meaning neither patients
nor doctors

will know who is getting
the drug.

Inside knowledge or expectations
could taint the results.

If there's any kind of bias

which occurs in the trial,

the trial results
could be null and void.

I'm going to start off
with asking you,

do you have trouble
with your memory?

Yes.

Patients like Bonnie

are given cognitive tests
similar to this one.

What is the date today?

I can't...

Okay, that's fine.

People with mild
to moderate Alzheimer's

cannot answer
many simple memory questions.

Now, I want you
to listen carefully

because I'm going to say
three objects to you.

And when I'm finished,

I'd like you to repeat
those objects back to me.

Are you ready?

All right.

All right, here they are.

Apple, penny, table.

Apple, penny, table.

All right, now try
to remember those

because I'm going to ask you
about them again

in a little bit.

Now, spell the word "world"
backwards.

L-R-O-W.

Okay.

Now, what were those three
objects I had you remember?

All right, any guesses?

No.

During the trial,

patients getting the placebo
are expected to decline,

serving as a control group.

If Bonnie gets the drug,

the hope is that her scores
will stay the same

or decline at a slower rate
compared to untreated patients.

People don't realize that
stability is a very good outcome

for a progressive illness
like Alzheimer's.

If there's no change over a year
or 18 months,

then it's a very good outcome.

Bonnie is beginning to enter

the moderate stage
of Alzheimer's.

She has stopped working because
she can't trust her memory.

I can't say it's good.

I have little bits and pieces
that come together,

and then I can figure out
what's going on.

We do have selfish reasons
for doing the study,

let's face it.

I want her back.

I want her the way she was.

But if she could stay the way
she is right now, I'd be happy.

I'll take what I can get.

I'll take it too.

Yeah.

But the outcome of the trial
hangs on key questions.

Will the drug stop plaques from
forming in patients' brains?

And if it does,
will this slow or halt dementia?

In Colombia, Genentech's drug
will also be tested,

but in a different type
of trial.

Working with the Colombian
families,

scientists will try
to prevent Alzheimer's

from striking at all.

So this is truly a unique
opportunity to intervene early

and show that you can actually
prevent the onset of symptoms.

So if you're doing
a prevention trial,

this is the ideal population
to use.

We know who's going to get
the disease, guaranteed,

and let's see if we can
prevent it in them,

and then you really know
whether your drug,

your treatment is working.

To see if the drug
can stop plaques from forming,

scientists will rely
on new advances in imaging.

Amyloid can now be tagged
with radioactive chemicals

so it appears in vivid color
in brain scans.

Eric Reiman used the new imaging
on the Colombian families

and made a startling find.

By doing these studies

in carriers of this
Alzheimer's-causing gene

versus non-carriers
from the same family,

we were able to detect
these brain changes

earlier than many people
expected.

The imaging captured
a "silent period."

Plaques, seen in red and yellow,

started accumulating in carriers
around age 30

and peaked some ten years later,

well before the onset
of symptoms.

It was a revelation:

plaques form
long before dementia begins.

Indeed, we believe that

everybody at risk
for Alzheimer's disease

begin to have the underlying
biological changes

two decades or more
before the onset of symptoms.

Now, that may sound frightening,
but that also provides

a window of opportunity
in which to intervene,

to strike at the disease

before the clinical symptoms
ever begin.

Reiman's work
became the catalyst

for launching the preventative
trial in Colombia.

Ramiro wants to sign up,
but he has concerns.

It's a five-year commitment,

and no one has taken
the experimental drug that long.

I was hesitant at first

because when you're
feeling well,

when you don't feel anything,
it's very hard to commit

before you know whether or not
you'll get Alzheimer's.

Over the next several months,

the families visit Dr. Lopera
to learn more about the trial.

So why have you been
invited here?

Because you're all members
of a family

at risk for a genetic disease.

To enroll,
everyone must be screened

to be sure they have
no cognitive impairment.

The trial includes people
who have the mutated gene,

as well as those who don't.

Half of the carriers
will get the drug.

Everyone else gets the placebo.

And nobody will be told
his or her genetic status.

I remember so clearly a case of
a 24-year-old boy who I asked,

"If we can tell you whether
or not you have the disease,

would you want to know?"

He said, "Yes, I want to know."

He said,
"If I have that mutation..."

And he did this.

He said, "I'll shoot myself."

Now, this kid is 24 years old.

He's got another 24 years
until he,

even if he has the mutation,
would get the disease.

Lots of things are happening
in that interval.

Genetic information is fire.

For participants like Hugo,
there are practical concerns.

One is taking time off from work
for periodic brain scans.

I had this form for my boss
to sign, giving me permission,

and he said, "If you want to be
a lab rat, go ahead."

But I just said thanks.

I don't fight with him.

Why?

I'm no rat.

It's an experiment
they're doing,

and it's for us,
so I don't worry about it,

because if they cure me,
they'll cure my children.

If Hugo carries the mutation,

doctors expect to see
plaques forming

long before symptoms occur.

And if he is a carrier
and receives the drug,

and if it's successful,
at the end of the study,

we hope to see that
the first scan

has a lot of amyloid,

the second has less amyloid,
and the third has much less,

or is almost free of amyloid.

Only independent experts will
know if the drug is working.

Everyone else,
including Genentech,

will have to wait until 2020
for results.

The drug company has to sit back
and hope for the best

while, essentially,

the fate of the drug
is in the hands of others

who are running the trial
and assessing the data.

So it's a long trial,
very expensive,

but likely to give you answers.

Back in the U.S.,

Genentech's mild to moderate
Alzheimer trial is ending.

I don't want you
to move your head at all.

I'll do all the moving, okay?

The scanning technique
used in Colombia was too new

to monitor everyone
in this study.

Bonnie is part
of a small group of patients

getting their final scans.

She doesn't know if she's been
taking the drug or the placebo.

But now that the trial
is officially over,

Bonnie and every patient
can receive the drug

for a period of time.

At times, I think her memory's

getting worse, and at times,
I think it's leveled.

And, I mean,
I can live with this,

I mean, every day
asking me what day it is.

He has no choice.

Exactly.

I'm hoping
this study is working.

This would be a miracle,
I mean, an absolute miracle.

At Genentech,
it's time to find out

if their drug has helped
patients with Alzheimer's.

The data from the trial will be
revealed in a private meeting.

The event is called
the "unblinding."

He's on the telephone.

There's so much human emotion
tied up in this.

Did you sleep well last night?

No.

Everybody in a company
is working so hard

to develop these drugs.

Hey Robert, how are you?

I'm fine, how are you?

Good.

Good Monday?

Yep, did you sleep well
last night?

I'm incredibly optimistic
that we may see something

that really will benefit people.

Senior Vice President Sean Bohen

knows success depends
on the trial's design.

When you test a hypothesis
in the clinic,

a lot of it is dependent upon
how you conduct the trial.

What do you measure?

How accurately and consistently
do you measure it?

It takes a lot time and,
frankly, money to get there.

Bohen hopes
the $350 million trial

will lead to a big breakthrough.

But even a hint that the drug
works in some patients

will be considered
a step forward.

The moment of truth.

If you took a poll of this team,

this team I think feels pretty
confident it will be positive.

Five, four, three, two, one.

I think it's going to be
more complicated.

According to the atomic clock,
it's 11:00.

For now, only the core team

will have access to the reams
of information collected.

It will take months
to analyze the details

and find out if they're
on the right track.

The results will be made public

at an international Alzheimer's
conference the following year.

As clinical trials forge ahead,
millions of patients

confront Alzheimer's
relentless progression.

Greg O'Brien struggles
with rapid mood swings.

You just feel like such
a dumb-ass, you know?

And I know I'm not.

I'm not stupid,
I just have a disease.

You know, I love my family,
I love my friends,

but I don't love myself so much
anymore.

I don't love myself so much
anymore.

I remember picking up his phone
months ago when it was cracked.

My dad said he dropped it,

but what he really did was
he didn't know how to dial

and he got mad and he threw it
against the wall.

If I thought his rage

was part of his personality,
how disturbing would that be?

And how angry would I be?

So when I see him upset
and angry,

I know that it's not him,
it's the disease.

Having watched his mother die
from Alzheimer's,

Greg knows what's coming.

You lose your self-esteem,

but you don't want people
to feel sorry for you.

So you fight back,
you fight back, you fight back.

While patients around the world
wait for a treatment,

scientists fighting Alzheimer's
convene in Copenhagen, Denmark.

At the Europa Cafe,
Sean Bohen and Carole Ho

prepare themselves
for a critical presentation.

Researchers from rival companies
and universities

are eager to hear
if Genentech's drug worked.

The Genentech team
already knows the answer.

Carole Ho recalls
the roller coaster of events

that led up to this moment.

So that day
when the door closed,

that was the first of actually
two unblindings from our data,

and this was the unblinding
actually of the low dose.

In the low dose group,

there's essentially
no difference

between the drug
and the placebo.

The low dose clearly failed,
but what about the high dose?

So fast forward a few months
after that,

we then unblinded the high dose.

And now we had all the data,

and all of a sudden,
that lens was just opening up.

In the high dose group,

there is a drug-placebo
difference

in the more mild patients.

While mild patients on placebo
declined as expected,

those taking the high dose

declined 35% less
on cognitive tests.

When I saw the data, the first
thing that came to my mind

was just this overwhelming
sense of relief that

in the milder patients
at the higher dose,

we saw some signals that suggest
we're having success.

That's incredibly promising
for earlier stages of disease.

But do the results
warrant spending

nearly a billion dollars
on a large phase three trial

for mild Alzheimer's patients?

After a few months, a decision
is made to move forward.

And in Colombia, where they are
intervening early,

they will switch
to a higher dose

to give the preventive trial
its best shot at success.

And, of course,
the people here in Colombia

are as mild as you can get.

They don't have symptoms yet.

So each trial stands on the
shoulders of the previous one,

allowing insights to proceed
as everything in science does...

incrementally.

In Cambridge, Massachusetts,
a biotech company called Biogen

set out to capitalize
on the lessons of past trials.

Its scientists designed
a selective

phase one safety trial,
hoping to get clear results.

Instead of treating
moderate Alzheimer's,

Biogen only enrolled patients
like Donna,

with mild or early stage
disease.

And they scanned every patient

to be sure they had plaques
that their drug could target.

The results
exceeded expectations.

It appeared that
the more drug that was given,

the more amyloid plaque
was removed from the brain.

And the longer that person
was on the drug,

the more plaque was removed.

So we believe we have proof
that our drug

is getting into the brain
and attacking the plaques

and reducing them.

Having done that, the next step
is really, does it matter?

Does that contribute
to improvement in cognition?

Now, I'm going to show you
a few common objects.

Although the primary aim
of the study

was to test the drug's safety,

Biogen also gathered
cognitive data.

What is this?

Pacifier.

What is this?

Screwdriver.

And what is this?

That's a good question.

I don't know.

I know what it is, but...

With only 166 patients
in the study,

it was too small to draw
definitive conclusions.

But a signal did emerge.

And there, we saw that

lowering amyloid
in the brain of mild patients

correlated with a slower decline
in cognition,

especially for the highest dose
of the drug.

In contrast to patients
on placebo,

those taking the high dose

declined some 80% less
on cognitive tests.

But there were side effects.

Things like edema,
or swelling in the brain.

So many of those patients
had to drop out.

So it's something
we want to avoid

because we have to make sure

people don't develop
any significant damage

from the amyloid removal.

And, unfortunately,
this side effect will limit

how much of these antibodies
we can give to people

as we're trying to help
their brains remove the amyloid.

For Tony Estrella,
the risk seems worth taking,

especially if the trial leads

to a successful drug
for his mother.

Where is that arrow?

Can you tell me
what that arrow is connecting?

It's connecting from 11 to 9.

Hm...

So you think you changed it
from 11 to 9.

That's why you crossed out
the nine.

I don't know.

You're looking for a lifeline
of some kind,

because it's unknown territory.

And so with that comes
a certain amount of fear

about what's going to happen
to your mom.

And all of a sudden,

you can't help but think
about yourself as well.

And my grandfather
had Alzheimer's as well.

And so you think about, "Well
this isn't gonna stop here,"

which makes this trial
so important.

Betting that the side effects
can be managed,

Biogen is taking the gamble

and jumping directly
to phase three trials,

treating thousands of patients.

We are in the midst of testing

a hypothesis that the world
has been challenged to test.

We think this is
a very viable target.

It may not be the only target.

And huge investments are
at stake.

A lot of time and effort's
at stake.

We're looking for a signal
somewhere,

a signal that would show that
we're on the right track.

And in the last couple years,

a small signal
is beginning to emerge,

suggesting that these
antibody therapies

may provide us with a treatment.

The key to success appears to be
giving these antibodies early.

Reisa Sperling thinks
clearing plaques

from the brains of baby boomers
might avert an epidemic.

She's running a preventive trial

for people at risk
for ordinary Alzheimer's

using a drug developed
by Eli Lilly.

In past trials,

it slowed memory loss 34%
in mild Alzheimer's patients.

So this suggested to us that

if we could go
even ten years earlier

in people who barely have any
symptoms or no symptoms at all

and slow cognitive decline
by 30%,

we could really prevent dementia

in a large proportion
of individuals.

Most of those people
would die out ballroom dancing

instead of in a nursing home.

So I didn't have
a heart attack or anything?

You are doing just fine.

Go ahead and sit up.

Art Canter knows that scans have
detected plaques in his brain.

He also fears his memory lapses
may not be normal aging.

So he's joined
the preventative trial.

You can be the ostrich,

you know, if you want
to stick your head in the sand

and just say, "Well,
whatever happens, happens."

So yes, it's high stakes
for all of us

who are going through
this whole process,

but at the same time,

there's the potential
of what they might find

in whether or not the meds
will work.

While preventing plaque buildup
may keep Alzheimer's at bay,

Sperling suspects this approach
won't help everybody,

especially as
the disease advances

and another culprit identified
by Alois Alzheimer

over a century ago,
begins to wreak havoc: tangles.

It's been known that
two different changes happen

in the brain of people
with Alzheimer's disease.

One is the build-up
of amyloid into plaques,

and the other
is what we call tangles

that accumulate
inside the nerve cells.

Tangles are made of a protein
called tau,

which help stabilize neurons
and allows them to communicate.

Yet in Alzheimer's disease,

tau is corrupted
and twisted into tangles.

As tangles form and neurons die,
the symptoms of dementia set in.

But why does tau go bad?

Insights are coming
as new advances let scientists

image and track tau

in the brains
of living patients.

So, the first thing we found

when we started to look
at tau scans

is that almost everybody
over the age of 65 or 70

has some tangle buildup
very deep in the brain.

Now, these are still
normal people,

but at a certain point
in some individuals,

the tau just is transformed.

It tangles.

It proliferates, it propagates
into other places in the brain.

It just spreads like crazy.

And the reason becomes obvious
when amyloid and tau scans

from the same person
are compared.

In Alzheimer's disease,

people don't get tangles
spreading throughout their brain

unless they have amyloid.

So currently, we think that
amyloid pulls the trigger

and tau is the bullet

that unfortunately kills
the nerve cells.

And when that happens, now
people begin to get demented.

So if we're gonna have
a treatment,

you can't ignore tau.

This is a complex disease that
needs a multi-pronged attack.

Now we're seeing the first drugs
going into clinical trials

to stop the tangles
from spreading,

but we don't know what problems
they're going to see.

Coming up with the right therapy
that's safe,

gets into the brain,
it's potent,

hits the right target,
this is part of drug discovery.

It's incredibly hard.

As tau drugs enter testing,

Genentech, Biogen, and Lilly
await the results

on their antibodies
targeting amyloid.

Even if they slow dementia,

they will not be silver bullets
or help everyone.

Still, experts predict
we may see the first drugs

to treat the cause
of Alzheimer's by 2020.

But progress also depends
on getting people

to join clinical trials.

It really is a very promising
time for the field,

and I think that's one thing

that patients
should keep in mind,

is that if we can enroll
these trials in half the time,

we get the answers
much, much sooner.

There's only one way out of this
problem, and that's research.

And the research community
is really active,

and the insights
are coming rapidly.

And that is where we're going
to get an answer.

There we go.

Bonnie can no longer be
left alone.

Since her husband's
sudden death,

her daughter has moved
back home to help.

After 16 years of illness,
Yolanda passed away.

But many of her relatives have
entered the preventive trial.

They want to find
a way to break that chain,

and they want a better future
for their children.

It's the first time in 30 years
they've had any hope.

To prepare for his future,

Greg is selling
his Cape Cod home.

Alzheimer's is like having

a sliver of your brain
shaved off every day.

And you get up the next day
and you say to yourself,

"Okay, where am I
gonna be today?"

And it is scary.

I don't know what's going
to happen,

I don't know who's going
to show up.

I've got to get it together.

And I don't know when that light
in my brain's going to go off.

But I want society to take this
disease, Alzheimer's, seriously.

This is hell on wheels,
and it's racing right for us.

This NOVA program
is available on DVD.

NOVA is also available
for download on iTunes.