The following script is from “The Alzheimer’s Laboratory,” which aired on Nov. 27, 2016. Lesley Stahl is the correspondent. Shari Finkelstein, producer.
Nobel-prize-winning Colombian novelist Gabriel Garcia Marquez once wrote of a mythical town in the middle of the jungle whose residents suffer from a mysterious affliction that erases their memories. Today, in a region of Colombia called Antioquia, reality appears to be imitating fiction -- in a way that may answer questions for all of us.
For more information, visit the Alzheimer’s Prevention Registry, a registry anyone 18 years or older can sign up for. It provides news about Alzheimer’s research and trial opportunities that people may qualify to participate in. It’s led by the non-profit Banner Alzheimer’s Institute.
View a list of ongoing Alzheimer’s studies, including the study that Stave is participating in.
Antioquia is home to the largest concentration in the world of people who carry a rare genetic mutation that makes them 100 percent certain to develop Alzheimer’s disease. And as devastating as Alzheimer’s is anywhere, this is a particularly cruel version -- it strikes when people are in their mid-40s and leads to death about a decade later. It is a tragic situation, but a perfect scientific laboratory. And it’s now the center of a multimillion dollar, NIH-backed study trying to find out for the first time whether Alzheimer’s disease may be preventable.
These are the Andes Mountains and lush countryside of Antioquia, Colombia, whose capital city, Medellin was once famous for murder and the drug cartel of Pablo Escobar. Today Medellin -- or “Medejin” as it’s pronounced here -- is peaceful. But for some families here, there’s still a battle going on, a battle against an insidious disease. This family, mother Cecilia, her seven children, and grandchildren, lost its patriarch, Alonso.
Freddie: For me, my father was number one.
Freddie, the oldest, remembers his dad always eager to join in and play with him and his friends.
Cecilia: He was a very joyful person. He loved to dance. He was a really nice person, a very good father, before the disease.
Lesley Stahl: When it first started, what were you noticing that made you think he’s-- he’s different?
Cecilia: He started asking, “What is the date today? Do I have to go to work?” And we got concerned.
Alonso at the time was in his mid-40s, so the memory loss and confusion made no sense. His doctor suggested exercise and vitamins, but Alonso just got worse -- forgetting the names of his children, getting lost and disoriented. His son Victor had to help him get dressed.
Victor: I gave him his shirt, I told him “Dad, come, I’ll help you put your shirt on” and the first thing he did was to grab it and put it on through his feet.
Lesley Stahl: Did he understand what was happening to him?
Victor: There were moments of lucidity where he would ask me and say, “Son, what’s happening to me? Why don’t I remember? I don’t remember my children, or my wife. I don’t know who I am.”
His son Julio took him back to see the doctor:
Julio: When I asked the doctor I told him “Doctor, I am not leaving here--” Sorry. “Until you tell me what is wrong with my father.”
The doctor sent them to Francisco Lopera, a neurologist at the University of Antioquia who knew exactly what was wrong with Alonso, because he’d become the local authority on a rash of early-onset Alzheimer’s cases in and around Medellin.
Francisco Lopera: They were getting disease very early in the life.
It all began many years earlier, back in the 1980s when Lopera was a young medical resident. He had read about small numbers of people scattered around the world who’d developed Alzheimer’s in their 40s. So when a 47-year-old man came into his Medellin clinic with Alzheimer’s-like symptoms, he was intrigued and decided to investigate.
Lesley Stahl: You met this one man and you decided to go to where he was from?
Francisco Lopera: I decided to go to the town where he was living.
Lopera learned that the man’s father and grandfather had also lost their memories in their 40s. Then, a few years later, another similar patient came into the clinic, this time a 42-year-old woman from a town 40 miles away. Dr. Lopera’s then-nurse, Lucia Madrigal, asked if any of her relatives also started losing their memories when they were young.
Lucia: They told us yes, that the father, the uncles, the grandfather, the great grandfather, so I started making a little family tree, on one page, and I showed it to Dr. Lopera and I told him “Look what we have here. What is this? So many with the same disease…”
And so began a detective hunt that lasted more than a decade. Lopera and Madrigal traveled all over the region, finding more and more people afflicted with early-onset Alzheimer’s and compiling family trees.
They thought it might be genetic, so Madrigal spent days at parish churches, poring over heavy ledgers where priests for generations had recorded village births, marriages, and deaths. Thanks to these meticulous records, she was able to trace the disease back hundreds of years, and to make an important discovery -- the different families were actually one huge extended family, connected generations back by common ancestors who had died young, with an unusual cause of death written down by the priest: “softening of the brain.”
This is what “softening of the brain” looks like in real life. Fernando is 46 years old, a descendant of that second patient years ago. He started forgetting things when he was in his late 30s, and now can no longer speak, feed himself, or do just about anything on his own. His aunt takes care of him round the clock just as she did with his mother when she got the disease at the same age.
Norelly is at an even later stage of the disease. Despite her appearance, she is just 58 years old. Patients were going from mild symptoms to complete dementia and then death within about a decade -- as Dr. Lopera showed us in these cognitive test results.
Francisco Lopera: You can see, at 38…
Even at age 38, this man struggled -- as many older Alzheimer’s patients do -- to copy a complex drawing accurately.
Francisco Lopera: At 45.
And things got worse from there.
Francisco Lopera: He lost more. At 50.
Lesley Stahl: Ah! Oh!
Francisco Lopera: At 51.
Lesley Stahl: Oh!
Dr. Lopera was convinced that what he and Madrigal were discovering was scientifically important, but even as they found more patients and more related families, he couldn’t get anyone outside Colombia to take notice. Until 1993, when a Harvard professor came to give a talk about Alzheimer’s in Bogota, several hours away.
Ken Kosik: There was a person in the audience, Francisco Lopera, who came up after the talk and said, “You know, there’s-- I have a family here that w-- has-- early-onset Alzheimer’s.”
Ken Kosik, now at UC Santa Barbara, was that professor.
Lesley Stahl: A family. Could’ve been four people.
Ken Kosik: It could’ve been just four people. But he started to tell me how many it was. And as I listened to him, I became just so absorbed and taken with what he was telling me that I changed all my plans, went with him to Medellín. And, we began a collaboration that goes on to this day.
They showed Kosik what Lucia Madrigal showed us -- the family tree they had compiled based on all that searching through church records, for just one of the affected families, going back all the way to the 1800s.
Lesley Stahl: This is one family?
Lucia: Una sola! (Only one!)
It just kept unfolding and unfolding. Covering these pages are small squares representing men, circles for women. The colored-in squares and circles mean the person got sick with Alzheimer’s at an early age.
Lesley Stahl: Look, she had these sons and a daughter. And then it just kept going down-- through the generations—
Ken Kosik: When we looked at the family trees, about 50 percent of the offspring were getting the disease. That’s a clear signature of a gene.
But what gene? Kosik connected Dr. Lopera with leading geneticists in the U.S., and they started collecting blood samples and searching. Within a year, a major breakthrough. They found a specific mutation in a gene on chromosome 14 – one tiny flaw in the DNA responsible for all this family’s suffering. The discovery was published in 1997 in the Journal of the American Medical Association. Lopera had identified the largest concentration of early onset Alzheimer’s cases in the world.
Lesley Stahl: If a person has that mutation, do they get Alzheimer’s?
Ken Kosik: Yes, they do.
Lesley Stahl: If they have it, they definitely get the disease.
Ken Kosik: Right. There are some mutations where you don’t definitely get it. But this is a bad one. And if you have this mutation, you get it.
For families like Alonso’s, discovering the mutation was a blessing – a crucial first step toward finding a way to fight the disease. But it was also a curse, because it meant that anyone whose parent had the mutation has a 50/50 chance of having inherited it too.
Lesley Stahl: Do any of you know if you have that mutation? Do you know?
Freddie: Nobody knows.
Lesley Stahl: Nobody knows.
Well, somebody knows. Dr. Lopera and his team have been testing for the mutation and compiling a database, but their policy is not to tell family members if they have the mutation or not -- and not even to reveal the results to Dr. Lopera -- since at this point there is nothing that can be done to help.
Cecilia: Sometimes I ask, which one will get it? But I throw that thought away, because I don’t want to think about that. I pray a lot to God that none of them gets it. I don’t want to see my children with that disease.
Lesley Stahl: Each one of you knows, because of your father, that you have a 50/50 chance. So what kind of a weight does that put on you, day in and day out?
Julio: I’ve even prayed to God that if there’s one person who has to have the disease, I say to God, “Let it be me.”
Sara: I thank God that I’m a nurse and that I would be able to take care of them, but I tell myself, “First I had to go through it with my dad, the experience of the disease, and I may have to go through it with one of my siblings, or with several, we don’t know.”
Sara told us she would love to have children of her own, but given her risk of developing the disease, she’s decided against it.
Sara: So that my children don’t have to go through my same experience.
Lesley Stahl: You’ve been working on this 30 years. How do you cope with all this pain?
Francisco Lopera: [breaks down]
It was not the response we had expected.
Lesley Stahl: It’s that hard? It’s that hard.
But Dr. Lopera knew that even in the midst of all this tragedy, there might just be a glimmer of hope. Because what he had discovered in these families -- hundreds of people destined to develop Alzheimer’s, and easily identifiable with a simple genetic test -- presented a unique scientific opportunity to test whether it’s possible to step in and stop early-onset, and maybe all, Alzheimer’s disease before it starts. That part of the story, when we come back.
Alzheimer’s disease is the sixth leading cause of death in the United States. More than 5 million Americans have Alzheimer’s right now, and given the aging baby boomer population, that number is projected to nearly triple by mid-century. Yet unlike many other leading killers, there is no effective treatment. An Alzheimer’s diagnosis is essentially a prescription for a slow descent into oblivion -- an inexorable loss of the memories, spatial skills, and ability to think that make us who we are.
Early-onset Alzheimer’s patients like the hundreds of family members in Colombia are a tiny fraction of the whole, but to scientists, they could be everything. Because they are offering researchers something they have never had before -- a way to test whether intervening years before people start having symptoms, might halt the disease in its tracks. Answers are still years away, but with more than a thousand Americans developing Alzheimer’s every day, a way to prevent it can not come soon enough.
The scene we witnessed in Dr. Pierre Tariot’s exam room at the Banner Alzheimer’s Institute in Phoenix is one that plays out in neurologist’s offices every day.
Dr. Tariot: So if I asked you what city we’re in right now, what would you say?
Norm: Uh, you know, right, I don’t know at this moment.
Norm, age 72, has been diagnosed with Alzheimer’s -- the typical, late-in-life form so many of us fear. It begins with mild memory and thinking problems and spirals into full-on dementia.
Dr. Tariot: Who is that young lady over there?
Dr. Tariot: Betsy. And is she a friend?
Dr. Tariot: How do you know Betsy?
Norm: Because I’ve been loving her for a long time.
Dr. Tariot: OK. Is she your sister?
Norm: A little bit of both.
Dr. Tariot: Uh-huh. Is she your wife?
Norm: I don’t think so. I think you’re-- somebody. I wish I was, but…
They’ve been married 51 years. Unlike early-onset Alzheimer’s, there’s been no single gene identified that causes this. No way to know who among us is destined to get it.
Lesley Stahl: What percentage of all people are going to be get Alzheimer’s?
Pierre Tariot: One percent of us 60 or older will have a dementia like Alzheimer’s disease. But by the time you hit 85—
Lesley Stahl: What percent?
Pierre Tariot: --that-- that percentage is approaching 40ish percent.
Norm: That’s a Dogan and these are Gogans.
Pierre Tariot: Alzheimer’s disease has been called out by the World Health Organization as the coming pandemic of the West. We have to do something to put it behind us.
Claudia to female patient: Can you draw the numbers for a clock?
But Dr. Claudia Kawas, a leading Alzheimer’s researcher and clinician at the University of California Irvine, says she’s frustrated that she can’t offer her patients any hope.
Claudia Kawas: I have to say I’ve been doing this now for a third of a century. And when I started, I just never would have believed we would still not be closer than we are now to making a real difference. It has been a little disappointing.
It hasn’t been for lack of trying. Kawas gave us a quick primer on the tell-tale signs of Alzheimer’s in the brain after autopsy.
Claudia Kawas: Every place you see a brown spot, that is a senile amyloid plaque. In contrast, you see these black things that tend to be triangular shape. Those are what we call neurofibrillary tangles.
The relationship between plaques and tangles isn’t completely understood, but because it’s been shown that amyloid plaques build up in the brain before tangles -- and years before patients develop symptoms -- pharmaceutical companies have spent hundreds of millions of dollars since the early 2000s developing drugs to remove amyloid from the brain, and hundreds of millions more to test those drugs in patients like Norm.
Lesley Stahl: Of all the trials that have been done, what percent have succeeded?
Pierre Tariot: About one percent.
In other words, a resounding failure.
Lesley Stahl: So what does that say, do you think?
Claudia Kawas: Well, it says either amyloid is not the right thing to go after. Or it says we need to remove it earlier on in the process before it’s made all the other things cascade after it. You know, if you give a polio vaccine once somebody has polio, you can understand why it doesn’t work.
Lesley Stahl: You’re saying that maybe those drugs haven’t worked because the person already had Alzheimer’s?
Claudia Kawas: Exactly. And maybe if we give ‘em early enough, it might work.
But how can you test drugs on people before they develop the disease, when you don’t know who among us is going to get it? Dr. Tariot and the executive director at the Banner Alzheimer’s Institute, Dr. Eric Reiman, realized there was a place where you could know who was going to get Alzheimer’s --- Antioquia.
Ken Kosik: And that’s when my phone began to ring.
By then, Ken Kosik had been studying the Colombian extended family for 15 years.
Ken Kosik: Received a call from the people at Banner. And they said, you know, “You have this family. We know when they’re gonna get it. We know who’s gonna get it. Can we start treating before the disease strikes?”
Kosik connected Tariot and Teiman with Dr. Lopera, who by that time had identified hundreds of people who carried the gene mutation, guaranteeing they would be struck with Alzheimer’s in the prime of their lives. Reiman and Tariot traveled to Medellin and met with both healthy and sick members of the extended family.
Lesley Stahl: Is this particular family, in the world-- extraordinary?
Pierre Tariot: There’s nothing else like it. The idea that there’s this concentration within roughly 100 miles of each other is-- just an extraordinary phenomenon.
And a perfect scientific laboratory. To lay the groundwork for a large clinical trial, Banner flew a group of extended family members from Medellin to Phoenix for PET scans. One goal: to compare the brains of those with and without the mutation years before any memory loss began, when they were in their 30s. Dr. Reiman showed us the results.
Eric Reiman: This is somebody who doesn’t have the gene. They have no plaques in the brain.
But in members of the family with the mutation, it was a different story.
Eric Reiman: Extensive amyloid deposition in the brain.
Lesley Stahl: That’s the red.
Eric Reiman: Red is more amyloid. But yellow is also amyloid.
This brain had even more. The images showed that amyloid plaques build up in the brain more than a decade before memory loss begins.
So if a drug could remove that red and yellow, maybe the disease could be prevented. Banner developed a plan for a multimillion dollar drug trial and convened a meeting with leading scientists, pharmaceutical companies, and representatives of the NIH.
Pierre Tariot: The end of the meeting, each scientist was allowed to say one closing thought. And Francisco had the last word.
Lesley Stahl: Lopera?
Pierre Tariot: And he paused a long time. And you could hear a pin drop in the room.
Francisco Lopera: I said to them-- “We w-- the families are waiting for you.”
Lesley Stahl: They’re waiting for you.
Pierre Tariot: That’s the point when, you know, the goose bumps came, and we said, “We really have to make this work. We really do.”
And they did. With a commitment of $15 million from NIH, another $15 million from philanthropists, and the rest from drug company Genentech, the trial -- on an immunotherapy drug to remove amyloid plaque -- enrolled its first patient three years ago, and they’ve been enrolling more people ever since.
Freddie: They told me about the study and I said yes. I’ll go right away, and anything that you need it, I am here.
Freddie and all his siblings signed up. The plan is to enroll a total of 300 members of the extended family who are healthy and have no memory loss yet -- 200 who have the mutation and another 100 who don’t. That way, no one will learn their genetic status just by being accepted into the study. Of the 200 with the mutation, half will get injections of the drug; the other half will be injected with a harmless placebo.
The study is double-blind: neither patients nor investigators will know who’s getting what. They have to come in every two weeks, for at least five years -- long enough to see whether the group taking the drug does better than the group taking placebo. Final results aren’t expected until 2021.
Lesley Stahl: Is this the first time in all these years of seeing these patients that you can actually offer them hope?
Dr. Lopera: Yes, this is the first time. Because in the past we only offer them education-- better quality of life but no hope to have a solution. And now they have hope, a big hope.
Lesley Stahl: What would be the best outcome?
Pierre Tariot: Nobody who receives the immunotherapy experiences any worsening of their thinking or memory ability. Doesn’t change at all. Doesn’t decline. That would be fabulous. That’s a stretch goal.
And that would be just the beginning.
Claudia Kawas: If it makes a difference for them, I think there’s a reasonable chance it could make a difference for all the rest of the people who get Alzheimer’s disease.
And that of course is the ultimate goal: to help prevent the late in life form of Alzheimer’s that we’re all susceptible to. The hope is that one day every one of us could be screened and when necessary, treated before problems begin.
Claudia Kawas: It might be the case that just like when you go to your doctor to get your cholesterol checked in your blood to see if you need drugs to lower your cholesterol, you would go, and get an amyloid PET scan, and-- it would be part of—
Lesley Stahl: Routine.
Claudia Kawas: --routine prevention.
Lesley Stahl: What if the drug removes the amyloid, and they still get the disease?
Claudia Kawas: I think that’ll mean that there are other things we need to be targeting besides amyloid.
Lesley Stahl: But will you say that the drug test was successful?
Claudia Kawas: Hard as this is to say, yes. I think that we need to know the answer.
The answer to whether the field’s focus on amyloid plaque removal for the last 15 years has been a failure. If this test doesn’t work, they will at least know they need to go in a different direction.
Lesley Stahl: You know, Victor, all the other drug trials that have gone on for years have
Lesley Stahl: You know that.
Victor: But this is going to be the exception. This is the exception.
Lesley Stahl: If it does work, this saves this community.
Ken Kosik: Wouldn’t that be amazing?
Lesley Stahl: That would be amazing.
Ken Kosik: To me, I am always impressed that these families that come from such a remote area of the world-- have the potential for informing all of us, globally, about a path forward for conquering Alzheimer’s.