Transcription
[Music] I have walked through many lives, some of them I own, and I am not who I was, though some principle of being abides from which I struggle not to [Music] stray.
The brain in old age, in its furrows and folds, dwell the imprints of a lifetime, the unique history that makes us who we are. All we know and can remember at in 100 billion neurons—cells that can last our entire lives. Neurons can live to 120 some years. What else will work for that long without going to the repair man all the time? I think what’s unusual about the aging brain is the fact that it’s built to withstand, you know, that many years. Somehow these neurons just keep going. And neurons are up against a potentially hostile environment; they take hits. In its final decades, the brain must contend with the slowing down of its neural circuits and with crippling diseases and injuries few younger brains ever [Music] face. But scientists have begun to unlock the secrets of the aging brain, long thought to be defenseless to the onslaughts of time. The brain can marshal surprising powers of renewal. [Music] [Music]
Three years ago, a stroke left Kent Miller with the left side of his body paralyzed. Even after months of rehabilitation, he still can’t use his left arm and hand. His career as an accountant has come to an end. “You know, you feel worthless; you can’t, you can’t do the things that you used to do, physically and mentally, and it’s been a bear for my wife. My family hasn’t been too easy for me either. I want to become whole; to put it simply, I want to get my arm back. I want to take something in my left hand. I want to be able to tie my shoes. Is, is that, you know, isn’t that ridiculous? Sixty-three years old and can’t tie your own shoes. I’m sick of Velcro; I want shoelaces, and I want to be able to tie them.”
“What about using a toothbrush to brush your teeth? Did you use the affected hand to do that?” “No, I didn’t do that. You just use your right hand.” “Yeah.” “When you were getting dressed, putting your arm through a sleeve of clothing, do you actively push your left hand and arm through, or do you pull it on with your right hand and arm?” “I pull it on with my right.” “So that means your left hand just kind of sort of laid there?” “Yeah.”
At the University of Alabama in Birmingham, Kent has enrolled in a study that may help him regain the use of his arm. “For Mr. Miller, um, he’s still there very much cognitively, but physically he would like to have his independence back, so we’re trying to work with him so that he can regain some of his independence.” “You know, actually, that’s fairly flexible.” “Yeah, I know, but I can’t do it.”
The stroke that left Kent with a paralyzed left arm struck at the part of his brain responsible for moving the arm. A blockage in an artery suddenly stopped the flow of blood, cutting off oxygen, shutting down the flow of signals. Millions of neurons were killed. Millions more were injured. The damaged part of his brain shrank to half its former size. Because the right side of the brain controls the left side of the body, Kent’s left arm and leg were paralyzed. “Most patients have been told after a stroke that the amount of movement that they have at 6 months or one year is the maximum that they’re going to have for the rest of their life. Whatever they have at one year, that’s it, and they’re not going to get any better. Okay.” But neuroscientist Edward Taub and his colleagues are teaching stroke survivors from all over the country how to revive the stricken part of their brains, breathing well many years after a stroke. “Let it go. Let it go. Ex- extend that finger on out. Good job.” “There are little spacings in here for each individual finger, so you’re going to have to push, push your hand all the way in.”
Taub’s innovative therapy requires Kent to immobilize his good hand. “No, let’s do this again. What it boils down to is you can’t use the good one, so you got to use the bad hand. Okay, you ready to place your hand up on the table?” “Yeah.” Kent, written off his left hand as useless, now he will discover just how much he can do with it because of the resilience of his brain. During the past 3 years, many of the injured neurons have recovered, but most have been recruited by neighboring brain circuits responsible for moving parts of Kent’s body unaffected by the stroke. Yeah, if Kent works hard enough, can force his recovered neurons to resume their old job and send signals to his left arm once again. But first, he has to overcome a dependence on his right arm that’s become deeply encoded in his brain. “The person could use the arm if he really tried, but he just never tries. He doesn’t try because he’s learned not to try. It’s a conditioned response, but it goes on week after week, month after month, and as time goes on it becomes more and more powerful, and eventually it becomes overwhelmingly powerful, and so you’ve got to counter condition this extremely strong tendency not to use the arm.” “I want you to see how many of these dominoes you can flip over in 30 seconds. The key is to not just pick them up and drop them, but to actually use your fingers and maneuver the domino. I know you have the ability, and that’s what I’m here to do, to push you to do the right thing. Okay, let’s go.” “You starting the timer?” “Yes.” “O, o. Try it again. That one was two. That’s okay. This last one you just did here, we don’t want that. Better. That’s great. Those fingers are working. Yeah.”
What makes Taub’s therapy so effective and so exhausting is that these small, all clumsy movements have to be endlessly repeated. “Nice, easy for you to say.” “Yeah.” Over the next two weeks, Kent will flip hundreds of dominoes. Simply overcoming this nonuse of the limp isn’t enough; you have to repeat movements over and over and over again; that’s the secret. “Come on, fingers. That’s all right. Keep going. You put grease on this one.” Hundreds of Taub’s patients have seen remarkable improvement. James Fa was a sales manager when a stroke paralyzed his right arm. “I had no use of it whatsoever; it was just dangling. I even had thoughts of maybe talking to somebody about amputation because it was just in my way, really.” But after 2 years of paralysis, he went to see Edward Taub, and his life turned around. “Two weeks or three weeks after that program, we were out to eat dinner one night, and I looked over at my wife, and her eyes were wide and her mouth was a gasp, and I said, ‘What’s the matter?’ And she said, ‘Look at your right hand,’ and I did, and in that right hand was a steak knife, and I was cutting up my steak as if nothing had ever happened to that hand.” Encouraged by his progress, Fa continued his exercises for years. “I have no problem doing anything I want to do with my right arm. I can drive my car. I can tie my shoes. I can brush my teeth. I can shave. I can do anything I want to do.”
The human brain is an enormously plastic instrument. The amount of area of the brain that is involved in producing movements or receiving sensation keeps changing continuously based on the amount of use that part of the body gets, and it turns out that no matter how old the person becomes, no, no matter how aged the brain is, that plasticity remains undiminished. Taub has found that after just 2 weeks of therapy, the part of the brain that controls the crippled limb has expanded back to its original size. Just why is still a mystery. “In introductory psychology courses when I first went to school, they used to say some people think of the brain as a muscle, and that was invariably followed by the professor laughing and saying the brain isn’t a muscle. Well, the fact of the matter is that in the last 15 years what we’ve begun to find is that in a sense the brain is like a muscle, and the more that you exercise it, the better it gets.” “Well, those good French fries, yeah, they’re pretty good.”
After two weeks of therapy, Kent Miller is eating with his left hand for the first time in years. “Break my neck getting to it though. Good, good. That’s good, good bite. I know I’m a lot farther along than I was because I really wouldn’t use my left hand. When your hand gets tired, stop, let it rest. It was so much easier to use the right, which worked normal. Finger now it’s, it’s almost natural for me to use it at times, the left side. How’s that? That’s a little bit better. One thing I got to watch is that I don’t bite my fingers, yeah, cuz you kind of want to keep those. That’s another thing; it’s easier to go down after something than sometimes lift the arm and up to where, where it is. One of the things they want me to do is to comb my hair, and I just can’t hardly get up there where I can get to my mouth. Okay, and that’s [Music] neat.”
“In this task, I’m going to say some words that are the names of objects and animals. When listen carefully, and when I finish, I want you to say them back to me in the order of their physical size, so from smallest to largest. Waste basket, oven, river, slipper, lemon, slipper, waste basket, oven. I— what the third, what the last one you said there, I forgotten already.”
While only some of us suffer from strokes, all of us worry our minds may start to fail as we get older. “I’d like you to point to the same blocks in the same order. Here’s the first one.” This lab at the University of Michigan studies how age affects mental performance. Its director, psychologist Denise Park, is gathering evidence that presents a new view of brain aging. “Aging begins in your 20s, as soon as you reach maturity. Our data show clearly, absolutely clearly, that um, as you age from 20 to 30 you’re a little bit slower, you process information not quite as fast. All um, you can hold a little bit less information in consciousness, and you recall a little tiny bit less from 20 to 30, and from 30 to 40 the same thing, and so on and so forth. Then suddenly you’re 70, and you start really noticing perhaps that these continuous declines have aggregated, and you may realize that you’re not cognitively what you used to be. Now this is especially true of memory, and the more unfamiliar the information, the more trouble you’re going to have. You’re going to remember familiar stuff, but if I bring you in my lab and ask you to remember a list of words, you’re going to see that age-related decline. Okay. This task is the free recall task. In this task, I’ll read you a list of 12 words. When I get to you should listen carefully to the words, and when I get to the end you should recall them back to me in any order that you like. Okay. Okay. All right. Line, honey, train, sky, puzzle, jury, garage, doll, wife, toast, bed, watch. Recall. Line, honey, train, sky, doll, um, honey, um, watch. Honey, train. I said that, didn’t I? Watch, toast, doll, wife, honey, line.”
“Learning someone’s name, remembering where you parked your car, jury comes to mind. Why do these things get harder as we get [Music] older?” One answer may lie in the way new memories are formed. For a memory to take shape, neurons must forge electrical and chemical links that connect them into a stable circuit. For decades, scientists thought that as the brain aged, millions of neurons died, making it harder for new circuits to form. But in the 1990s, this longstanding theory was found to be wrong. “One of the most remarkable things now that we understand it is how little nerve cell loss there is, how much the brain stays full of cells that we need in order to function normally, and that’s something that we didn’t used to know at all. Now this is interesting because it forces us then to look elsewhere for, for the changes in the brain that are impacting function.”
“Hey guys, how’s the cutting going?” “Great. These the uh, brains from Boston, yeah.” At Mount Sinai School of Medicine in New York, neurobiologist John Morrison is looking for clues in a region of the brain where new memories are formed, the hippocampus. “When we learn something new, neurons in the hippocampus forge strong connections by sending electrochemical messages across the tiny gaps between them called synapses. Essential to the strength of the connection is the movement of electrically charged particles of calcium drifting through the synapsis. When the particles stream into a neuron, they trigger chemical changes that make the connection more reliable. The calcium flows through a molecule that’s the gateway to the neuron, the NMDA receptor. We know that the NMDA receptor was critically linked to memory, so one of the changes that leads to memory decline in aging might be lower levels of NMDA receptors, so we have looked for those kinds of changes.” When Morrison examined the hippocampus of monkeys, he found that in young animals a single synapse had dozens of NMDA receptors, but in older monkeys the numbers of receptors dropped sharply. “Well, it was really amazing because this decrease occurred in the circuit that leads to the ability to learn and remember new things, the classic form of memory that’s affected in aging. This is to me an optimistic scenario because now we have a molecular target that could potentially be manipulated to restore the health of that memory circuit.” “You guys can start staining for the light microscopy.” Morrison is trying to develop drugs to replenish the lost receptors and rejuvenate failing memories. “So that’ll give us a receptor and a pre, pre-synaptic marker.” But the brain, scientists are learning, has ways to rejuvenate itself. Ninety-three-year-old Milton Adamson has exercised regularly since he was 42. On memory tests, he does as well as people half his age. “I feel that the mind uh, does not lose its ability as quickly if you exercise.” “We never used to think that physical activity was good for the brain until really very recently, and there was a large study that was done where they took over a thousand people in the community and looked at the things that predicted what helped them maintain mental ability, and it turned out that physical activity was one of them.” “Yeah, well we’ll get involved with that in the next week or so because I just got a call today from Burns, nent asked me to be present at the next meeting, which is a week from Thursday.” Milton has been tested at the University of California at Irvine this afternoon, where scientists are searching for the biochemical keys to successful aging. “Okay, the biggest revolution is we’ve gone from describing what’s going wrong to getting deep down into the mechanisms to tell what can you do about it and how can you put more quality into the life of a neuron.”
Carl Cotman theorized that exercise might help to keep neurons healthy by boosting production of vital brain proteins. To test his theory, he compared two groups of rats. While one group sat idly in their cages, the other group spent hours a day running. “They jump into these running wheels, and they go like gangbusters around, and they even do little tricks in the running wheels, and then you say, well, what happens is the brain out after 8 days?” Cotman found that in the running rats, levels of a protein that helps neurons grow, called BDNF, had doubled in a part of the brain that’s critical to memory. “The surprising bottom line is that exercise will induce all kinds of wonderful molecules that keep neurons healthier; they keep them stronger; they’re basically molecular fertilizer, and running actually increases uh, these molecules in the brain.”
As knowledge of the aging brain deepens, a new portrait is emerging of an organ that’s resilient and resourceful, whose lifetime of experience may provide it with a unique advantage. “Younger people seek out more information, and that’s what they’re good at; they’re good at processing and seeking information. Older people are good at mulling over situations, reflecting and, and using and drawing upon their experiences, and I think that’s what wisdom is.”
Stanley Kunitz is America’s poet laureate, still writing and reading his poems, a mentor to younger poets. He is 95 years old. “How shall the heart be reconciled to its feast of losses? In a rising wind, the manic dust of my friends, those who fell along the way, bitterly stings my face. Yet I turn, I turn, exalting somewhat, with my will intact, to go wherever I need to go, and every stone on the road precious to me.” “Mr. Kunitz, that was absolutely wonderful.” “There we are, and here’s your lovely pen.” “Thank you.”
“We were really in the woods 20 years ago; uh, we didn’t understand the fundamental nature of brain aging. We thought that to get scile, to sort of lose your marbles as you got older was just a normal part of life. That’s really not how brain aging works.” “It was such a great pulse of life, affection coming back from that audience; it was hard to resist, and I loved hearing about your mother, Stanley.” “If all of my patients were like you, I’d be starving.” “Thinking about you sometimes a name slips you, that, that seems to be the most, or you don’t remember where you put something down. Little occasional bits of memory uh, vanish from the screen. On the other hand, some memories go deeper than ever before; they are profoundly embedded in your whole psychic structure; they form a constellation that is at the center of your imagination.” “Summer is late, my heart. Words plucked out of the air some 40 years ago when I was wild with love and torn almost into two, scatter like leaves this night of whistling wind and rain. It is my heart that’s late; it is my song that’s flown.”
Some people’s brains will age slowly, some will age more rapidly. A big factor is the genetic factor, what’s built in. The other factor is the maintenance of activity, and if the aging person remains active, there is ample evidence to indicate that his intellectual functioning will decrease at a much slower rate, and maybe not decrease at all. “Poetry is an exercise of the spirit, the spirit within one, and every time you exercise it you increase your [Music] vitality.” Most people aren’t poets; they may enjoy poetry. So what do they do if they’re not poets to stay vital and connected and uh, as alive as you are, to care about the life, to care about others, to remain active. “For example, you plant the seed, you cultivate the soil, you watch it grow; you’re participating in an ancient ritual of life [Music] itself.” “I kneel to the crickets trilling underfoot as if about to burst from their crusty shells, and like a child again marvel to hear so clear and brave a music pour from such a small [Music] machine.” “What makes the engine go? Desire, desire, desire.” [Music]
As scientists learn more about how the aging brain works, they are overturning some of the central dogmas of neuroscience itself. For decades, neuroscientists believed that neurons in a fully developed brain never reproduce themselves and can never be replaced. “The idea was that the brain is a very complex structure; it’s involved in learning and memory and storing large, large amounts of information, and if you were adding new neurons into the circuit over time it would somehow disrupt the function of the brain.” But in 1998, at the Salk Institute in California, neuroscientist Fred Gage and his colleagues discovered that even into old age, the human brain continues producing new neurons, like the neurons that form a baby’s brain. They are created by the division of stem cells, the seeds from which the tissues of the body grow. “Everybody was astonished that our brain makes new nerve cells late in life. The assumption was that you had all the nerve cells you were going to have when you were younger, and then you would lose them, and you would never be able to replace them.” Stem cells in an embryonic brain are wildly prolific, producing hundreds of different kinds of neurons, enabling us to see, smell, walk, think, remember. But in an adult brain, very few neurons are produced; most stem cells mysteriously stay inactive. As neuroscientists look to the future, they have begun asking if these stem cells can be directed to make neurons to replace those killed by injury or disease. “And that’s very exciting because it opens up the idea that the brain is not this fixed machine for which there are no replacement parts.” “Look at my fingers, where they’re almost touching.”
At Harvard Medical School in Boston, Dr. Jeffrey Macklis works with patients with neurological disorders. Forty-eight-year-old Sally Carlson has Parkinson’s disease. “Okay, look over at the frame again,” which typically begins in middle age and grows steadily worse as a person gets older. “Now can you open your eyes again and walk over there? Can you do it on the, on the tightrope?” Deep inside her brain, in a region that coordinates movements, thousands of neurons are slowly dying. Sally’s body is starting to feel stiff; her hands sometimes tremble. “Folding clothes is probably the worst thing; it’s a constant reminder, cuz obviously with three kids I’m folding a lot of clothes, but I can’t shake things anymore. I can’t shake a pillow into a pillowcase. I can’t just— pulling up is a very difficult thing to do.” “I think you’re in shock when you first find something like this out.” “Yeah, scared to death, and, and I know I’m not dying, but part of me is dying; there’s no doubt about that.” “We love you.” Macklis can relieve some of Sally’s symptoms with medications, but not forever. “Ultimately, 10 or 20 years down the road, there are going to be enough neurons that have died that no combination of medicine is going to be fully effective.” “Now how about doing a padding on this side?” She’s understood from the very beginning that our goal is to get her through the childhood of her children, to their graduations and weddings uh, before we start losing the efficacy of the drugs that we currently have. “Now can you put your fingers, your hands out, palms straight up, and spread your fingers apart? By the time Sally reaches her 60s, she may have trouble even walking.” “And then back to where they are.” But Macklis hopes that someday science can develop a treatment to restore her lost abilities by tapping the potential of stem cells. Different. Macklis is not only a doctor; he’s a research scientist. “These are normal adult sections. If there’s a possibility to replace and interconnect new neurons within circuitry that’s imperfect, that gives a whole different view toward repair of the nervous system.” For an individual animal, they ran two different to identify the forces that trigger stem cells to become neurons. In 1999, Macklis and his colleagues launched an ambitious experiment; they targeted the most recently evolved part of the brain, the cerebral [Music] cortex. In tests with mice, they injected a chemical killing thousands of neurons, but within weeks the decimated neural circuits received some unexpected reinforcements, a stream of stem cells. They moved to exactly the right location; they turned into the right kind of neurons, and most strikingly, some of them could send long connections to the correct targets. In other words, they rebuilt circuitry in the brain. For the first time, scientists had shown that a living brain might be able to repair itself with new neurons. But it may take decades before scientists know if neuron replacement will ever be effective in people. “Lots more work to get there, lots of work in the laboratory in animal models, but what these experiments clearly tell us is that there exists some sequence and some combin of molecular signals that can induce the birth of new nerve cells, and by finding out what these molecules are in mice we might be able to find out what the proper molecules are for humans.” The same mysterious forces that propel stem cells to build the baby’s brain may one day be harnessed to mend the aging brain. “I am extremely hopeful and would want to be the first human following the last rat or mice, whatever it is. We have such incredible abilities as human beings that I believe in miracles, and I have no intention of quitting before the miracle happens.” “I’ll wait till you finish, and then I’ll ask you. Okay.”
While Parkinson’s disease cripples the body, the most widespread disease of the aging brain is one that cripples the mind. These men and women in a California day center can still express themselves with pictures, but the parts of their brains that put thoughts into words are slowly dying. They have Alzheimer’s disease. Alvin Johnson was running an insurance company when he began having problems with his memory 8 years ago. He can no longer sign his name; he doesn’t know the date, the day, the time. “One weekend our daughter was here, and he walked into the kitchen and he said, ‘Who are [Music] you?’” Alzheimer’s disease is almost a uniquely human disorder because the areas of the brain most recently developed through evolution that are important for thinking and memory and reasoning are the most vulnerable. “It’s a tragic illness; it robs an individual ultimately of his own qualities that make him…”
Human, that you can set it down if you want. K, don't have to hold it. That's great.
Chuck Hyatt, a retired aircraft engineer, was always good at fixing things. "At least I get some rest tomorrow," he said. But two years ago, when he was 67, his wife and daughter began noticing a change. Sitting around, not doing anything, he was having trouble coordinating details or remembering what he'd done. Just the Hyatts want to know if Chuck's continuing difficulties are just a normal part of aging or the early signs of Alzheimer's disease.
"Yeah, unfortunately, the only conclusive proof of Alzheimer's comes after death, from analysis of brain tissue," the doctor explained. "You know it'd be great if we had a test that would tell us whether somebody has Alzheimer's disease—take an image of the brain, or take a blood test, or even if we had a reliable test of the spinal fluid—something to tell us absolutely certain: you have it or you don't. We don't have that test. So the way we make the diagnosis is based upon information from the examination of the patient and information from the family about how the person has changed. We're here to talk about your husband. Tell me what you've noticed about his memory."
"Well, I guess to start with, um, he just can't remember short-term things. Um, a lot of repetition is required in telling him something."
"Does he depend more on you for help?"
"He depends on me for help, and that's a change from before—big change. I mean, he was an engineer, he was a problem solver, and um, that just is not what it was."
"H, want to use this? Cuts real well. Yeah, you hold it up. Nope. Now we got stuck again. It has to be… it might be difficult to convince a casual observer that he has lost memory and thinking ability without the background from his wife. Certainly, his family is concerned about his decline. Tell me about your memory, any problems with memory?"
"Uh, definitely. I end up, uh, forgetting things. I'll, uh—D will say something to me, and half an hour later or something, I can't remember what she said."
"Are these important things, or…?"
"Sometimes they may be, but almost always there's not. Just conversation…"
"She was telling me something that… I guess I'd like to hear a little bit more about it from you about the Rams. You're a football fan, I understand you enjoy the games."
"Oh, yes."
"What's the last game that you've attended?"
"Uh, Rams versus 49ers."
"49ers, and how they won?"
"41 to… No, 21 to… no… was it 41 to 20 or something like that? But I'm not sure of that. I think that's what it was, or maybe 20 something… 41."
"Now, who's the, uh, the coach of the Rams?"
"No, that I don't know. Um, I'll think of it maybe right now."
"Well, if it comes to you, you let… let me know a little bit later."
"Yeah, sir."
"I want to ask you some questions just to test different things about memory and so forth. Some of these questions may be easy, some may be a little more difficult. Tell… tell me what year it is now."
"I say… [Music] 19… 96. I don't know… 96."
"What month is it? And you can guess, you can guess."
"April."
"April. Subtract three from 20, and then keep subtracting three from each new number all the way down."
"20, 17, uh, 14, 11, 8… no, seven… no, five, 2."
"Did very well. I didn't think too well. You took a little while to get there, but you got there. Most people… when you say Alzheimer's disease, get a mental image of an incapacitated patient, almost perhaps ready for the nursing home. But people don't overnight change from healthy, functioning older adult to a nursing home patient. There's a gradual change. Now, I don't know how confident you are about remembering things like the players and the coach. I bet a few years ago you would have known that without any problem whatsoever, and now you can't come up with it when you need it. So I think that kind of memory disturbance is not part of normal aging. It is not part of aging. I think it is a memory decline caused by disease, and… and the disease that most often affects us as we get older in this day and age, I would say that almost always that's Alzheimer's disease, and it should be treated because now there are drugs that help stabilize things where they are now. There aren't any drugs that will cure it. We don't have those certainly now, but compared to where we were even 5 years ago, there's been a tremendous amount of advance, and we hope that that pace will continue. It should do. I do too, for my sake anyway. Anybody… any other people that's going to follow me, right?"
"How as hell when you can't remember things…"
"Here we're looking at… guys… see? Then this is a really diffused deposit here, and here's a good diffused one. This is actually representative of almost all… all three stages in labs all across the world. Neuroscientists are closing in on the mystery that has baffled them for nearly a century: what causes Alzheimer's disease?"
Alzheimer's disease ravages the brain, killing billions of neurons, leaving in its wake dark, twisted filaments called tangles and large, sticky masses called plaques. For decades, scientists had no idea where they came from. It took so long to figure out the beginnings of Alzheimer's disease because the brain scientists who understood what Alzheimer's looked like under the microscope didn't think that these plaques and tangles were going to turn out to be the key to the disease. They thought they were tombstones of the process. But in the 1980s, scientists took advantage of new technologies to look more closely. They began to suspect that tangles and plaques were more than just tombstones—they were killers. Neurons depend for their survival on long chains of molecules arrayed like railroad tracks that transport nourishment across the cell. What keeps the track stable are short strips of protein called tau that work like railroad ties. In Alzheimer's disease, the tau mysteriously starts to curl and tangle, causing the strands of molecules to separate and collapse. "These things become twisted, and they just don't transport very well," a scientist explained. "You know, it's like somebody took the train track and went, 'Yeah… you know, try and get a train to run along there.' It just can't… falls off. If the material can't get where it needs to be, the cell is really going to collapse and eventually die." Looking at a cell late in the course of Alzheimer's disease, you see a cell that's literally choked with tangles of tau. Now, tangle formation is a long, slow process, that may be a very good thing, because if we can interfere with tangle formation early in the disease, what we may be able to do is prevent the progression of the disease. Neuroscientist Peter Davies thinks he may have found one of the triggers that causes tangles to form: a protein inside the neuron called Pin1. It binds to tau and bends tau—actually changes the shape of tau. "What we would like to do is to test the idea that if we block the effect… action of Pin1 on tau, will actually stop the tau becoming abnormal and becoming… becoming tangle tau." Davies has begun work developing a drug to block Pin1. But while he and others take aim at tangles, another group of scientists is targeting plaques. In the spaces between neurons drift thousands of molecules of protein. In an Alzheimer's brain, some of them are suspicious protein fragments called beta-amyloid—sticky and resilient bits of beta-amyloid clumped together to form an expanding mass called a plaque, which attaches itself like a barnacle to the outside of the neuron. Sensing a hostile invader, the brain's defensive cells fight back, releasing powerful chemicals. But the counterattack backfires—the chemicals set off a series of reactions that slowly destroy the neurons. "When the brain tries to defend itself from beta-amyloid, it seems to not get it quite right; it seems to cause even more of a mess." As the damage spreads, more and more neurons die, leaving whole regions of the brain infested with plaques. "It doesn't perfectly comigrate with any of the other… v… a little bit… so these are… these are her stable trans…"
Scientists like Dennis Selkoe theorize that lowering the amount of beta-amyloid in the brain may prevent Alzheimer's disease, just as lowering levels of cholesterol prevents heart disease. The trouble is that it's not so easy, because number one, the theory might be wrong—it's a hypothesis, not a fact—and number two, even if it's right, it may be troubled to lower amyloid; it may cause side effects. But experimental work that's been done in many laboratories worldwide supports this hypothesis strongly, and the proof will come from lowering beta-amyloid in people and watching their Alzheimer's get better.
In a pharmaceutical lab near San Francisco, neuroscientist Dale Schenk has taken a step toward that goal with a strategy that surprised many scientists. The novelty was to use the immune system to treat Alzheimer's disease—to try to tell the immune system, in fact, that this plaque material in the brain is foreign, and our immune system needs to get rid of it. Schenk developed a vaccine made from beta-amyloid itself and tested it on genetically engineered mice bred to develop plaques like those in Alzheimer's disease. "Well, as it turned out, to our huge surprise, when we immunized them from a young age onward and then looked at an old age when they should have a lot of plaque lesions, they had almost none; their brain was almost entirely perfect." Encouraged by his findings, Schenk wondered if the vaccine might eliminate plaques that had already formed in older mice. He vaccinated one group of older mice but left a control group untreated. He found that the brains of the mice in the control group were ravaged by plaque, but the brains of the vaccinated mice had almost no plaques at all.
"In the beginning, I was skeptical, and then I saw the data, and the data are very good, and they're very persuasive, and that's why everybody's very excited." But establishing the safety and effectiveness of the vaccine and other new treatments for Alzheimer's will require years of testing.
"I'm hoping at least I can hang on long enough that… get somebody can make a breakthrough to figure out how to take care of this stuff. Right now, I really don't have much fear. I think that what concern though is… is the future. What's 5 years from now, or 10 years from now?"
"Okay, I'm not going to cut any more today."
"I really thought that in my lifetime I wouldn't see effective treatments for Alzheimer's disease, and I believe now that in my lifetime I will."
Let me start hearing this in… okay… in my darkest night, when the moon was covered and I roam through wreckage, a nimbus-clouded voice directed me: "Live in the layers, not on the litter." Though I lack the art to decipher it, no doubt the next chapter in my book of Transformations is already written. I am not done with my [Music] changes.
Take a 3-D animated tour of the brain at PBS online. Find brain teasers, take a cognitive test, and more at pbs.org. [Music]
Major funding for The Secret Life of the Brain is provided by the National Science Foundation—America's investment in the future. Funding is also provided by Pfizer. "We're spending nearly $5 billion a year looking for the cures of the future. We have 12,000 scientists and health experts who firmly believe the only thing incurable is our passion. Pfizer: Life is our life's work." The Medtronic Foundation, on behalf of Medtronic, providing lifelong solutions for people with chronic disease. Medtronic: When life depends on medical [Music] technology. The Park Foundation, dedicated to education and quality television. The Dana Foundation. The Corporation for Public Broadcasting, and by contributions to your PBS station from viewers like you. Thank you. [Music]