Hi, I’m Gregory Petsko. I’m Professor of Neurology and Neuroscience at Weill Cornell Medical College in New York City where I direct the Alzheimer’s Disease Institute. Today, I want to tell you about the coming epidemic of Neurological disorders and what we are trying to do about it This is my grandson, who was one year old when this picture was taken four years ago And that’s his great-grandfather, who was 87 when this picture was taken four years ago. I barely knew my grandparents. They died in their 50s, which is when people born in the 19th century typically died. But young people born today – they are going to know their great-grandparents and that’s something new. When my grandson was born, he was born into world in which only a handful of countries, which I have colored here in blue had more than 20% of their population over the age of 65. that’s the world we live in But when my grandson is 40, the world he is going to live in is going to look like this Why is this happening? It has never happened in human history. Why is it happening now? It’s happening now for two reasons. One is the life expectancy of people on this planet has been increasing steadily since the middle 1800s and shows no sign of leveling off In fact during the 20, 25 minutes listening to this lecture, your life expectancy will have increased by 3 minutes You can thank me later for that if you’d like Now here is another reason that it’s happening. If you look into the 1800s, check the bottom of this picture. You’ll see that the average woman had 5-6 children and the life expectancy, on the y-axis, under 40. But as the 19th century rolls along, the different countries of the world, they are colored coded here They start to move, and the life expectancy increases, and as it increases fertility rate drops Now as we get toward the end of the 20th century, We begin to see a crowding of the entire world in the upper left corner of this image and now we have a life expectancy above 70 for most countries in the world and the average woman has two children What’s the consequence of that? One is that the world has reached peak children. There are two billion children in the world, and there will 2 billion children in the world in 50 years and possibly 100 years. It looks like this is pretty much leveled off That means that the working age population is actually decreasing That has profound consequences One of those consequences has to do with the way we have constructed our civilization This is the other consequence, because you see though the working-age population has slowed down, the number of children is leveled off. The fastest growth demographic, at least in the United States, happens to be octogenerians or above you can see the little green bar there, that’s when I was born, there was only 2 million people in the U.S. Today the yellow bar, 12 million, almost By the time my grandson is 40, the red bar – 32 million people over the age of 80, in the U.S. alone. Here is the result of those trends on the last two slides For 20 thousands years or more, we have constructed our civilization on the assumption that the demographics resembled a pyramid That’s the far left image on the slide. What you can see is that there are always a lot of young, healthy people working, so they could support the very small number of sick old people at the top of the pyramid but as you can see today, the pyramid has started to change shape by the time that my grandson is 40, the pyramid is going to be a column and you are going to have as many unhealthy old people as you have healthy young people and our economic structure is not capable of supporting that so we have got a choices, we could have global thermal nuclear war or worldwide plague But somehow you never really have those when you just really need one *joking* Which leaves us with choice number 3, biological research We have to figure out a way to make the people at the top of the pyramid, all those people I have been telling you about we have to figure out how to make them healthy. We do that, we can handle this If we can’t… Here is one reason why that’s such an enormous problem Because age is the biggest single risk factor for most of the bad stuff that happens to you, I’m afraid This includes cancer, and heart disease, and lots of other problems What it really includes is neurodegenerative diseases If you look on the left of the slide, you’ll that Alzheimer’s disease and Parkinson’s disease go up exponentially once you reach well unfortunately my age, that’s about when they take off that’s also true of ALS or Lou Gerrig’s disease, although that has the peculiar effect of dropping off once you reach about the age of 75. We don’t know why that is true. Still, what this means is that all those 80 year old people that we’re going to be producing will be at risk for those diseases in fact if you are lucky in fact to live in your 80s, you have a one in two chance of being unlucky enough to have one of these Alzheimer’s Disease is the most prevalent of all the neurodegenerative diseases that’s the one I’m going to be focusing on in this talk and what you can see from this, is that Alzheimer’s Disease has been increasing rapidly as population increases. Sometimes, I’m asked whether there are environmental factors, diets, and other things that are producing this increase maybe they play some sort of roll, but we don’t have any real reason for believing that’s true it really looks like age and the population increase of older people are primarily responsible for this this is an enormous problem for us because it looks like half a million of new cases of Alzheimer’s and dementia will be diagnosed in the U.S. alone this year that’s about one every seven seconds and no known treatments alter the course of the disease. This is one of the few things for which we have no treatment whatsoever So this is why I call it an upcoming epidemic. We have 5 million with AD in the U.S. today By the time my grandson is 40, there will be almost 14 million people with AD That is the population of the state of Illinois, including Chicago Worldwide, if dementia were a country, 45 million people in the world today, greater than the population of Canada and by the time my grandson is 40, the worldwide population with dementia most of which is Alzheimer’s, about 70-75%, early and early onset dementia, that would be the population of Russia or Japan or Mexico In fact, it would be the ninth most populus country in the world by 2050. So here’s some numbers, there are about 5 million people in the US today. For Parkinson’s, divide that number by 4. For ALS, divid that number by 150 or so. The predicted to be 15 million people by the time my grandson is 40 More than 300 million worldwide by the end of the century, that’s the population of the United States There are 3 care givers for every patient by average. That means by the end of the century, there will be 1 billion people directly affected by 1 disease by Alzheimer’s Disease. My father told me you couldn’t understand Russia in the World War II period until you remembered that during WWII, every family in Russia lost a relative, statistically By the end of the century, just about every family in the developed countries will have a relative affected by AD And that will color everything about how we live. And in the US, 1/7 of the AD patients actually lives alone, which is a national disgrace in my opinion And the total cost for diseases like this is staggering For AD plus Parkinson’s plus ALS, we’ve got a total cost of over $100 million Some people estimate to $200 million a year, that’s more than cancer plus heart disease put together And by the time my grandson is 40, by 2050, the total cost for these diseases will exceed a trillion dollars a year And that’s out of a gross domestic product that will be around $20 trillion a year We can’t spend 1/20 of our GDP on one disease It will bankrupt society, we have that law to find a solution to this problem So what I’ve just described is just about a comet about to hit the earth And if you knew a comet is about to hit the earth, then wouldn’t you expect people everywhere would be clamoring for government to do something about the comet? And governments will be doing something about that comet? And if you believe that, then I’m afraid you are somewhat naive Because for this particular comet, governments are not doing nearly enough Look on the left of this slide and you will see the number of cases of AD is 4-5x that of HIV/AIDS But the amount of research funding for AD is 4-5x less than HIV/AIDS I’m not saying we are spending too much money on AIDS research, quite the contrary What I’m saying is what amount of money we should be spending on AD research We are not spending nearly enough. One of the reason now AIDS is a disease you can live with is because we spent enough money on research Brought lots of people in the field, we are not doing that for AD I calculate we need to calculate federal funding for this disease by at least 4-5 fold But we’ve elected in this country to spend most of our money on care rather than cure In fact, we spend about 9x more on medical care for people with chronic diseases than we spend on research to try to get rid of those chronic diseases. And if that makes sense to you, then try to explain it to me, because it doesn’t make much sense to me as far as the good of society is concerned. Well diseases that are neurodegeneerative, like AD, are in fact 6th leading cause of death in the developed world and the only cause of death that has been going upin the past decade, for all of the others, it’s been going down That’s what happens when you don’t do enough research and you don’t find a cure So I hope I’ve sufficiently frightened you, because this should frighten a saber tooth tiger in to thinking this is a problem we need to do something about scientifically. Let me set that stage broader in the rest of the talk About 110 years ago, Alois Alzheimer a young neurologist in Germany was presented with a patient Auguste Deter, Ms. Deter was suffering from dementia, and she was in fact the first patient who was diagnosed with what we call Alheimer’s Disease You might not know it looking at her, but she was 51 years old. AD is a disease of aging, but it’s not necessarily a disease of the aged. There are hundreds of thousands of people in the US who has AD before the age of 65. Auguste Deter got Alheimer’s in her 40s because she had a mutation in a particular gene, called Presenilin and that mutation met she was doomed for early-onset AD She was in fact dead in fact about 3 years after this picture was taken When Alois Alzheimer autopsied her brain, he found things that shouldn’t have been there. One was outside of those neurons, and he called those senile plaques and you can see them here, these were the original pictures that he drawn, the senile plaques They contained aggregated protein, we now know they contain fragments of a larger protein, that fragment is called A-beta, and that larger protein is called APP Inside the dying neurons, they saw tangles of a different protein We now know that protein is tau, and it’s a microtubule associate protein Similar aggregates of different proteins is found in the brains of patients with many neurodegenerative diseases – Parkinson’s Disease, Frontal-temporal dementia, mad cow disease, Huntingson’s Disease, and so forth So the phenonmenon is somewhat of a common one, even though the proteins do differ from disease to disease and the regions of the brain also do differ from disease to disease But these are as a category, a protein misfolding disease they are diseases in which a normal protein that should fold up into a wonderful tightly compact functional structure, doesn’t do that instead forms a peculiar beta sheet structure called amyloid that in turn lead to a variety of other structures such as oligomers, fibrils, or the dense tangles of fibrils that form these macroscopic structures I was telling you about now if you look at the plethora of species that’s being produced, it’s hard to tell the toxic specie that’s killing the neurons in these diseases The consensus is that it’s the oligomeric species, but that’s not established completely That’s really still a hypothesis, the genetics of these disease are fascinating, mostly all of them are etiologically sporadic and etiopathic that is to say they pop up randomly and we have no idea what causes them 10% of roughly each of them, 10% of Alzheimer’s cases, 10% of Parkinson’s cases, 10% of Lou Gehrig’s cases, are genetic they are inherit in a family in an autosomal dominant fashion, for AD, it’s virtually always autosomal dominant And the genes that are responsible rarer familiar dieases, which is the kind that Auguste Deter had She had a mutation, which ran in her family, and she got it as a consequence These particular genes, give us a tremendous clue as to what’s going on with a molecular and cellular pathology And that brings me to my final point, we made some progress against this disease, quite a lot of progress because the familiar form of the disease has lot us about about the biology of this disease much as cancer has began to be a treatable disease once we understand the molecular basis for cancer so we’re finally reaching that point with AD, and the human genetics has been a tremendous aid to that still remember what I told you at the beginning of this video, we have no way to treat it, huge cost, we have a colossal unmet medical need why is there any reason to think we can crack this problem even when we can understand it better? there are a number of reasons why I’m encourage, but the biggest reason is because of Mr. Douglas Whitney of Port Orchard, WA You probably heard of the Mexican beer commercials of the most interesting man in the world? Forget him, This, Douglas Whitney, is the most interesting man in the world, for sure, why? Well the Whitney family has lived in the suburbs of Seattle for many many years, and during that time, about half of the Whitney’s died in their 40s and 50s of AD, because the Whitney family had a mutation in the same gene that Auguste Deter had that mutation you’re guaranteed to get AD in your late 40s and die of it in your 50s that’s what happened to Douglas Whitney’s mother, brother, it’s what happened to seven of his closest siblings It’s inevitable, it’s an autosomal dominant gene, you have the mutation, you are going to get AD and die Doug Whitney is my age, 67. Doug Whitney, has the mutation. Doug Whitney is fine. What else does Doug Whitney have? if we knew, we’ll be a lot of closer to beating this disease. We don’t know yet, but I think we will. But that’s not the point, the point is that if Doug Whitney, who by the laws of genetics, had to have AD, and should have been dead 15 years ago If Doug Whitney doesn’t have AD, nobody has to get AD We can beat this thing, and we will. Thank you.