Curing Alzheimer's with Science and Song | Rudy Tanzi & Chris Mann | TEDxNatick

[Music] I'm going to talk to you today about an 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 of stopping Alzheimer's disease so first 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 stage my good friend Chris man 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 forgotten 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 unraveling I suppose then nothing's worth getting and everything is lost in its time 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 in this world won't you please please remember me you remember 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 you again 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 forgotten and lost in this world won't you be remember remember me remember you remember me 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 remember knees remember me we men remember me [Music] thank you very much never give up never give up [Music]

Channel: TEDx Talks

Views: 72,007

Rating: 4.8852715 out of 5

Keywords: TEDxTalks, English, United States, Health, Big problems, Brain, Cognitive science, Disease, Genetics, Medicine, Memory, Mental health, Neuroscience, Research, Science, Cause, Entertainment, Music (performance), Philanthropy

Id: iuel1AFKSDo

Length: 25min 5sec (1505 seconds)

Published: Fri Mar 03 2017