[computer keyboard tapping]
[music plays]
[O'BRIEN:] I am fearful of the day
when I put my hands on the keyboard
and not know what to do.
This is a painful naked story
for me to tell,
but everything in my training as a journalist says "shame on you
if you don't tell the story."
[O'BRIEN:] Several years ago I started experiencing the symptoms.
Horrific short-term memory loss,
not recognizing people I've known all my life,
not recognizing places I've known all my life.
[TANZI:] Alzheimer's disease is the biggest unmet medical need
we have in this country.
At 85 years old, 40% of the population
are already showing signs of dementia, mostly due to Alzheimer's disease.
[O'BRIEN:] After my diagnosis,
I named my son power of attorney.
So we were out in Coronado for a family reunion,
and I said "Brendan,
I want to talk to you about my medical situation."
He said, "I don't want to talk about it, Dad."
So I started reading from the 50 pages
of my medical report.
And then I got to the diagnosis.
He grabbed my 50 pages of medical records.
He ripped them into a million pieces
and threw them off the balcony.
And I watched them fall like snow in the desert.
And then he buried his head into my chest,
and he cried like a little boy.
So I grabbed a plastic trash bag,
and I went down
and I picked up the remnants of my medical records.
And it was as if I was putting my present life and life
to come in a plastic trash bag.
[TANZI:] If we want to treat this disease,
first we need to understand it at its very roots.
If you could go into Greg's brain
15 to 20 years ago,
what you would have been seeing
is this accumulation of this little protein, amyloid,
that become plaques.
And as these accumulate,
this amyloid causes the nerve cells
in contact with it to make tangles,
these twisted filaments of this protein called tau,
that accumulate inside the nerve cell
and choke it from within.
And so now the neuron is dying.
What we believe is now happening is that as it dies,
it spits that tangle out and that tangle travels to a healthy nerve cell,
and starts to kill it by forming tangles.
For decades we argued about which pathology was more important,
plaques or tangles.
But, what we've learned about that processes now
is that both the amyloid that's accumulating
and the dying nerve cells
cause a reaction in the brain, called neuroinflammation.
You have little cells in the brain
called microglial cells
that normally are trying to clean up
all that amyloid as it's made.
But if they see too much cell death,
they switch from being housekeepers to being soldiers.
They cause inflammation.
They create free radicals--
these little oxygen-based bullets
that are killing nerve cells.
And then this thing just keeps ramping up,
like a vicious cycle: more amyloid,
more tangles, more inflammation.
You can think about Alzheimer's disease as a chronic inflammation
in the brain,
driven by pathologies that are causing chronic stress.
And as this disease insidiously moves on,
it robs you of yourself,
and your loved ones watch you there, physically,
but you're not there internally.
It's really hard to image any emotional toll
that's worse than that.
[O'BRIEN:] It's very stressful
to lose a thought in a second.
Two days ago the light went off
and I was with my son.
I didn't know who he was, where I was,
what day it was, and I was in a panic.
He calmed me, my son calmed me down, 'cause they know.
"It's OK, Dad.
You're here.
Today's the date and this is what you're doing."
[TANZI:] I don't believe there's a silver bullet
to solving Alzheimer's disease.
I think that if you want to treat the disease,
you have to hit all three pillars
of the pathology--amyloid, tangles and inflammation.
You probably need to treat amyloid 10 years
before symptoms, knowing that someone is in trouble.
If you want to slow the disease down,
you not only target amyloid,
but you stop those tangles from forming and spreading.
Third, since there is so much inflammation in the brain,
throughout this disease,
any drug you have that can address neuroinflammation,
you'd want to take that early, middle
and late in the disease.
Problem is. we don't have the drugs yet.
But we do have some very promising drugs in trials.
[TANZI:] To me, thinking like a scientist
in order to solve Alzheimer's disease
means that you should not be afraid to think big,
wildly creative, imaginative,
in the privacy of your own mind.
But then when you externalize that out to the world,
do so with discipline.
Do so with rigor.
Because it's your job
to treat your world in a way that addresses
truth and reality.
[O'BRIEN:] I know the denouement of this play,
and I don't want to take my family there.
And, uh, my family is, um...
excuse me. It's emotional.
[sighs]
My family is very important to me, OK?
I'm a father.
There's that instinct to protect,
and how do you protect when you know you're not gonna survive?
And so, I want to make these few years
ahead as special as possible,
take care of my family.
And then the instinct inside me, as
a journalist, is to tell the story.
I'm the canary in the coal mine.
This is a grueling, difficult,
stay-in-the-moment journey that I'm on,
and it's knocking the crap out of me.
But if I can see there's some hope in it,
then it's worth the journey.
[music plays]