absolutely horrendous and devastating
disease that slowly and steadily
destroys the brain erases the mind and
the entire time loved ones of the
patient can only watch on helplessly as
this horror unfolds I’m talking about
Alzheimer’s disease this is a quiet
thief in the night that relentlessly
robs from the patient first the sense of
identity personality and ultimately the
very essence of self it’s about the
worst thing you can imagine facing after
you’ve lived an entire life of wonders
and experiences with your loved ones and
if that doesn’t sound bad enough I’m
going to tell you that I’ve learned just
feel 35 years and the bad news is we’ve
been approaching this disease all along
we’ve made lots of mistakes but luckily
there have also been many victories and
many discoveries with those mistakes and
as scientists the really cool thing
about being a scientist is that the most
important thing you can do is learn from
your mistakes and learn how to do things
better and on that note I can tell you
that right now
based on our mistakes the opportunity
has never been greater to stop this
disease in this next generation in our
lifetime maybe even by 2025 and I want
to tell you about this story but I’m
also going to tell you that families
patients caregivers loved ones the
medical and scientific communities and
especially the FDA all have to talk to
each other work together and listen to
get the job done by the time I’m
finished speaking I hope you get the
same since I do that there’s a lot of
reason to be optimistic what the future
there are 5.4 million patients in this
country today and worldwide there are 50
million and that 50 million is going to
be the number we have in this country by
2050 if we don’t do something about this
disease because right now we’re treating
the disease with drugs that temporarily
effect the symptoms modestly modest
benefit for a short while now right now
the current lifespan is close to 80
years old we’re living longer than ever
but the problem is a lifespan has now
outpacing our health span especially the
health span of our brains all of modern
medicine has us living longer but is our
brain keeping up that’s what we have to
face right now we’re going to be in big
big trouble going forward and that’s
because 40% of people at 85 years old
have symptoms of Alzheimer’s disease so
think about that 80 is the life span
right now that’s going to go up to 85 40
percent is I mean everyone born soon is
going to have a 40% chance of getting
this disease especially such a
devastating disease and right now there
are 71 million baby boomers like myself
all in one big group heading toward that
risk age Alzheimer’s right now sucks up
one in five dollars of Medicare and
Medicaid and as these baby boomers age
that’s going to jump up to one and four
and then one in three and eventually if
we don’t do anything about this disease
Alzheimer’s will single-handedly
collapse our health care system
economically a disaster so this means
that all of us have to work together to
wake up and do something about it
Alzheimer’s began with dr. Alzheimer dr.
Louis Alzheimer described the case of
Auguste deter who was in a Bavarian
Asylum called Baron schloss which meant
castle of the insane they weren’t
politically correct back then about what
they call their institutions he said she
was a 55 year old woman with memory loss
paranoia delusions hallucinations and he
noted in his journal that she was often
found screaming in the middle of the
night these words
oh god I have lost myself and that’s
what this disease is see all of your
life everything you experience is being
recorded on a hundred billion neurons or
nerve cells in your brain trillions of
connections creating a neuro network
like a tapestry the tapestry of who you
are how you loved ones know you your
personality Alzheimer’s comes in and
slowly rips apart that tapestry thread
by thread never resting until the
tapestry is gone that’s what this
disease is and this is what you’re
hearing and August eat his words there
for 80 years
we only define the disease by what
Alzheimer described in her brain he saw
these plaques these big boulders of
clumps of stuff
that was good and sticky around the
nerve cells he said the nerve cells were
choked inside by tangles that were
actually causing the nerve cells to die
and he also saw that the brain was
reacting to this to all this pathology
and cell death with inflammation that
caused even more nerve cells and for 80
years all we could do was describe the
pathology so in terms of solving the
disease it’s like aliens coming from
space and wanted to figure out football
and they get to the stadium at six
o’clock and the game was at one o’clock
they find a helmet they find a football
they find maybe some dug up turf and
cleat marks and they say okay now let’s
figure out what football is right you
get some clues but you can’t figure it
out and it wasn’t until the 80s and 90s
when I was lucky enough as a student at
Harvard to find the first Alzheimer’s
gene the amyloid precursor protein it
makes the stuff that’s in the amyloid
plaques we found more genes in 1995
called the pre-sentence and it was
another gene found called a bowi
and once these genes were found now
finally we had windows into disease
finally we said we have some real clues
that we could grab on to their eye tell
us how this disease is caused and what
one does with genes is you come up with
drug targets and I’ll use an example
first heart disease we take for granted
that you have to keep your cholesterol
low but did you know that that began
with very rare families who had very
rare genetic mutations
that caused them to have high
cholesterol and when this was observed
the idea came about hey maybe
cholesterol has something to do with
heart disease and now of course we all
manage our cholesterol to avoid heart
disease in our futures in a completely
analogous situation with those first
genes I just showed you from the 80s and
90s taught us was that our cholesterol
so to speak at Alzheimer’s is something
called the amyloid beta protein we call
it a beta for short and it’s this little
tiny protein that gets extruded from
nerve cells it comes from a bigger
protein that gets clipped so picture a
piece of rope in your clip in two spots
and it gets extruded and over time if it
starts to accumulate and form plaques
the idea is that that causes the disease
that’s what all the genetics in the 80s
and 90s told us well so we tested that
the idea was if plaques caused a disease
the plaque should cause the tangles as
these twisted filaments to choke the
inside of the nerve cells they made of a
protein called tau the Greek symbol tau
so we tried to put these genes into mice
for two decades you put in these
Alzheimer’s genes that make the amyloid
plaques and the mice and then you wait
for the mice to get the tangles and rest
of the disease and yeah the mice get
sick but the mouse would have to say my
brain has lots of amyloid plaques but no
tangles so this led to so much confusion
people were fighting back and forth see
it’s not the amyloid it’s the tangles is
at the my toes of tangles what causes
the disease amyloid beta amyloid protein
is called B AP so there were two
baptists and then there were the talus
and they would fight grown men fighting
like children at meetings and it was
because we’re doing experiments and mice
and many of us argued very simply hey
you know what we’re not 150-pound mice
you know maybe there’s some difference
between a mouse and a human if you just
kind of look at them
why don’t you would it be nice to be
able to use a human brain well with the
advent of stem cells now we can build
human brains in a dish and this is
exactly what my colleagues at Mass
General did particularly do young
he was able to take stem cells from
humans human stem cells create nerve
cells you see there on the side of the
panel and now if you grow them in a gel
because the brain is like jello if you
grow them in a gel that mimics the brain
the nerve cells start interacting and
talking to each other and creating neuro
networks just like in a real brain and
if you put those Alzheimer’s genes in
the same ones we tried in the mice put
those into the cells and have them make
amyloid you see in the middle panel that
orange dot in the middle that’s a plaque
for the first time you can make a plaque
the plaque was being formed in a mini
little brain in a petri dish Alzheimer’s
in the dish human brain organoids but
the beautiful thing was it took about
six weeks for that plaque to form six
weeks versus you know decades in a human
and if you wait a little longer then you
see the tangles reowww tangles that kill
the nerve cells something we couldn’t do
in mice and if you use drugs that stop
the plaques in the dish in the brain you
don’t get the tangles so this said to us
yes finally debate over plaques cause
the tangles and that said to us well if
we can stop the plaques then we stopped
Alzheimer’s disease it’s that simple
right well we tried that and the answer
was nope every Alzheimer trial another
mistake every house on a trial that
targeted the plaques failed whether
you’re trying to turn off the spigot
turn off the amyloid production that’s
the brain overflowing with amyloid in
the middle or you tried to clear the my
doubt of the brain every attempt to do
so no improvement in cognition in the
patient’s failure after failure and
again this led to argument CD amyloids
not the right thing and then we realized
something because we had great
breakthroughs in brain imaging if you
look up top what you’re seeing there is
every time blue goes to yellow and red
that’s showing where amyloid is in the
brain now we can image and actually see
the amyloid in your brain and get an
idea of when D amyloid occurs and what
we learned was pretty striking the
amyloids building up 10 to 20 years
before any symptoms of
mention 10 to 20 years so if you follow
that that slope all the way to the left
you see the beta-amyloid goes up and
then when it starts to flatten out
that’s when does dementia it’s already
done its job the amyloid is already
built up and started the disease and so
then we’re going in there after emily
has already done it and saying don’t
worry we’re going to lower your amyloid
well horses out of the barn it’s
equivalent to this scenario here this is
poor guys having a heart attack and the
doc is saying it’s okay you just need to
clone your cholesterol right you had to
do that 10-15 years ago when you knew he
was on his way to heart disease you
don’t wait till the patient has symptoms
imagine and this brings up a point
imagine if we waited till someone had
symptoms of cancer organ failure or
waited till someone had congestive heart
failure and a heart attack to say okay
now you have cancer now your fault
disease right we don’t do that as soon
as you have a small tumor neoplastic
cell we say this cancer we have to treat
it when you start to see high
cholesterol and plaque around the heart
you say you’re starting heart disease we
have to treat it and so on the same
thing in AIDS when you have HIV you
don’t wait for symptoms of AIDS to say
you have AIDS but an Alzheimer’s disease
we wait until you have symptoms to
diagnose and treat the disease it’s like
how do we do that how’d that happen and
every other disease of Aging we stop it
with early intervention early detection
but in Alzheimer’s we diagnosed only
when you already have the disease and
then we try to bring you back that was
the big mistake amyloid is a good target
but you have to hit it early unlike cars
is using cancer we don’t treat the cause
early enough we need to stop those
plaques 10 to 20 years before symptoms
we can use brain imaging and biomarkers
now if patients who in people who are
asymptomatic or very mild mild memory
problems start to see whether it is
amyloid in the brain and that’s when you
treat you don’t wait until the horses
are at the barn and I think this gives
us great hope now that if we can
convince the FDA that this is the way
forward and there are many safe drugs on
the horizon we’re making them others are
making them safe drugs and therapies
that will bring that M
lay down we have to lower the bar a
little bit when we do trials we can’t
expect you’re going to bring somebody
cognitively back by hitting a pathology
to started the disease twenty years
before it’s good enough to lower the
amyloid there’s enough data now to say
come on let’s work together define
people early on who have amyloid
building up in their brain through
alarming levels and bring that amyloid
back down just like we do a cholesterol
heart disease that’s the turning point
right now like I said medical scientific
community Families FDA have to work
together to make this happen
now many people ask when I get to this
point well why do our brains make
amyloid why do we make it in the first
place and this is what I want to tell
you about a very exciting new hypothesis
that is arisen based on new data the
pathogen hypothesis and I don’t have a
lot of time to go into it but it appears
that our brains are not sterile living
in our brains are bacteria viruses like
herpes fungus like yeast especially as
we get older we’re getting more and more
little microbes and buggies living in
our brain and it turns out based on the
newest data that we have just published
that the plaques are actually there to
protect the brain when there’s an
infection even a low-grade infection the
amyloid plaques form around the herpes
or around the yeast of bacteria to trap
it and keep it away from the nerve cells
it’s trying to do a good job but then if
there’s too many of those plaques they
trigger the tangles in the rest of the
disease so this says that not only
tackle the amyloid early on but if we
can find out what types of microbes are
invading the brain we can hit those
early on as well
antivirals antibacterials etc the bottom
panel shows a herpes virus and then in
just 30 minutes or 2 hours you can see
amyloid plaque completely enveloping
that virus and that’s in in a mouse
brain or in the Alzheimer’s in the dish
so that says that we also have to be
careful when we hit amyloid with drugs
we don’t want to wipe it out we just
want to turn it down this in when this
happens I just want to show this one
slide that little red guy in the middle
you see the red guy in the middle he’s
eating that green strain coming out of
the green blob the green blob is a
nerves
and that green string is its axon it
goes to a synapse and what happens is
when you get this attack of amyloid and
bacteria in the brain those little guys
come microglial go crazy and eat nerve
cells
that’s called inflammation this is what
you have to stop in patients who have
the disease right now we have to stop
the amyloid plaques and tangles before
you even get there so now we have some
idea what to do with the right patient
right drug right time and then the end
what’s going to beat this disease as
early prediction based on family history
early detection with imaging of
biomarkers and early interventions not
that pathology before there are symptoms
just like we do for cancer heart disease
diabetes and we’re going to have to do
this all with a cocktail we’re going to
need to hit the plaques the tangos the
inflammation all of it I work closely
with the cure Alzheimer’s fund working
on all of these aspects and I think
we’re making great progress and I think
if we work together we’re going to beat
this disease I’ve actually never been up
more optimistic that we’re going to beat
this disease if we just take that out of
this in front of us and do the right
thing now and all work together to make
it happen now on the side until we have
those drugs what can you do I like to
use the acronym sleds sleds not that
you’re going to slide down but but get
eight hours of sleep learn so come to
Ted exercise at least 8000 steps per day
diet Mediterranean is the best omega-3
is very important stress try to meditate
very very beneficial so remember sleds
and that’s what we can do until we have
the right drugs now as I end on the side
I’m a musician I play often with with
Joe Perry of Aerosmith and I’ve played
in the last hours with the album this is
a Joe Perry on the Jay Leno Show looking
very suave and like a rock star and
that’s me in the back on the keyboards
saying what the heck am I doing here I’m
a geneticist but it’s but this what is
fun I also started a music app called
spark that it’s a music therapy app for
Alzheimer’s patients so I’d like to keep
music in my life and speaking of that at
this time I would like to welcome to the
thank you very much I have a strong
connection with Alzheimer’s both of my
grandmother’s passed away with forms of
the disease and my paternal grandmother
was diagnosed with early onset
Alzheimer’s in her late 40s so it’s
always been a very scary part of my life
so I was very very happy and excited to
connect with Rudy who I literally
cornered at the TV studio where we met
and demanded to learn as much about his
research as I possibly could not through
our connection with music and
Alzheimer’s we did want to write an
anthem of hope to raise awareness and
the song is called remember me we wanted
to write remember me from the
perspective of someone with Alzheimer’s
so that other people could relate to how
terrifying it is to live with this
disease and how crucial it is that we
find a cure by donating proceeds from
the sale of the song to Alzheimer’s
research we were able to take action a
step further with the help of cure
Alzheimer’s fund by producing a music
video and visual art piece for remember
me that very poignant ly portrays the
struggle of living with Alzheimer’s
through dance and music now at the time
I was playing the phantom of phantom of
the opera’ national tour so I was able
to implore my very talented cast and
crew mates who had a connection with the
disease to donate their time to the
cause as well here you can see us on set
creating the video our dancer our makeup
artist our hair department my wife who
directed Laura everyone donated their
time to bring this story to life here
are some still slides from the video you
can see a young woman in white whose
vibrant before the middle side which is
when she starts to show symptoms to the
upper slide when she’s fully lost in the
disease now what happened next is truly
remarkable when we posted our little
passion project on Facebook and YouTube
it was sharing and being viewed at such
a rapid pace that the live view counter
could not keep up people were sharing
the
video with their own remember me stories
about their families their connection to
the disease and a worldwide conversation
started you can see some of the the
press and some of the people sharing
their pictures of their loved ones with
the hashtag remember me right there
in short remember me struck a chord an
emotional chord with the community it
became a coping mechanism for families
and it really did become an anthem of
hope it was very very very powerful to
see so now we would love to perform
remember me for you now for all the
families dealing with this disease and
remind them that they will never be
I need someone to hold – hold on for me
– what I can’t seem to hold on to the
life we used to live is slipping through
my fingertips like a thread that’s
I suppose then nothing’s worth getting
when I can’t find the words that I’m
trying to speak when I don’t know the
face in the mirror
I see when I feel I’m forgotten and lost
I know they’ll come a day when I have
gone away and the memory of me will
faint but darling think of me and who I
used to be and I’ll be right there with
I hope I’m one thing worth not
forgetting tell me that you’ll never let
when I can’t find the words that I’m
trying to speak when I don’t know the
face in the mirror
I see when I feel forgotten and lost in
this world
I hope I’m one thing worth not
forgetting tell me that you’ll never let
me go when I can’t find the words that
I’m trying to speak when I don’t know
the face in the mirror I see when I feel
that I’ve lost and lo in this world won’t you please