The paisa mutation | Translation
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Translated by MC Editorial
[Daniel Alarcón]: This is Radio Ambulante from NPR- I’m Daniel Alarcón.
Let’s start at Medellín’s San Vicente University Hospital. The year is 1984 and Francisco Lopera, a neurology student in his final year, is going through his routine: receiving and registering the patients that are coming in.
[Francisco Lopera]: There was a patient in the emergency room. The family brought him in because he had lost his memory, his behavior was changing, and he could no longer work, as he was a farmer. He would get confused when he tried to . . . to milk his cows or do his activities in the fields. So, I decided to hospitalize him for some checkups.
[Daniel]: Francisco did some neuropsychological tests—memory, attention, concentration and even mathematical reasoning. Before studying medicine, he had been fascinated by the brain, how it worked, and the diseases that attacked it.
[Francisco]: What interested me was dementia, language problems, attention and concentration problems, reasoning problems, memory problems.
[Daniel]: So, he wanted to understand the way this patient’s brain was handling memories.
[Francisco]: When we evaluated him, I discovered that this patient had a memory disorder very similar to what was described in patients with Alzheimer’s.
[Daniel]: Francisco had studied Alzheimer’s at school and knew a few things: that it is the most common type of dementia; that it usually appears with old age, when spots form in the memory-related area of the brain. That in some cases, it appears sporadically, but in others it can be inherited. That mild symptoms appear first, such as spatial confusion, sudden forgetfulness or repeating questions.
The disease does not kill the patient, but in its final stages the person cannot make voluntary movements, not even walk or swallow, and that ends up causing more serious damage to the body. And there is no cure.
And, well, in addition to knowing the theory, he had also seen it up close. His grandmother suffered from Alzheimer’s when he was about 19 years old and was beginning his medical studies. It was sporadic, that is, there appeared to be no family history. They had taken her to various specialists, but nothing could be done. Very soon, she stopped recognizing her children.
[Francisco]: And so, I made a promise to myself that when I became a doctor, this would not happen to any grandmother—being unable to recognize her own children.
[Daniel]: That’s why he became so interested in this patient. Test results clearly pointed to Alzheimer’s . . .
[Francisco]: The one thing that didn’t make sense to me was that he was very young—the patient was 47 years old. Alzheimer’s usually begins after age 65.
[Daniel]: And he had never seen that. Francisco investigated further and found something that intrigued him: There had been some cases in the world of young people with Alzheimer’s, but the cause was unknown. Talking with the patient’s family, he learned that both his mother and one of his grandparents began to lose their memory at that same age. Although they were never diagnosed, they died with very similar symptoms.
The diagnosis that Francisco and his colleagues reached was hereditary early-onset Alzheimer’s dementia. But there was nothing more they could do. They sent him home with recommendations for taking care of him. Because there is no cure for Alzheimer’s, the only thing doctors can do is prescribe something for sleeping and to control anxiety, depression or aggressiveness.
Even so, Francisco did not detach himself from the case, and decided to travel to the town where this man lived. He wanted to search for more answers. But at the time, he couldn’t do much more to solve the mystery. He was just a student and had no way to do more in-depth brain tests.
He just collected all possible data on symptoms, the context in which they lived, their ages, and some time later, with an agreement not to reveal names, he wrote a scientific article together with three other colleagues who worked in the same hospital, to leave a public record of the strange case.
Shortly after meeting that first patient, history repeated itself. A woman arrived at the hospital with similar symptoms. This time she was admitted by a nurse, Lucía Madrigal . . .
[Lucía Madrigal]: A patient in her forties who had . . . Well, she was acting strange. She had changed. The family said that she couldn’t remember anyone, that she recalled a lot of things from way back, but she couldn’t remember recent things.
[Daniel]: She came from a town in the same area north of Medellín where the first man who had obsessed Francisco came from. Lucía already knew about that case, and the next day she told Francisco everything. The woman appeared to have Alzheimer’s . . . and, like the other patient, she too was early onset. It was too much of a coincidence that these very strange conditions occurred in two people from the same area.
[Lucía]: I asked him what we could do. And he said, well, no, the thing is that we have no way to work. We would need to have a project to be able to do it, money.
[Daniel]: Francisco was intrigued, but it seemed like a risky bet. At that time, the mid-1980s, very little was known about why Alzheimer’s occurs, and much less about this strange early variant. As in the first case, they lacked the resources to investigate in depth. They couldn’t do detailed studies of the brain or DNA analyses, but their intuition suggested that in these people’s brains there could be valuable answers to better understand Alzheimer’s. Francisco asked her if she was interested.
[Lucía]: So, I started pulling the thread of the data that they had given me and I got to work.
[Daniel]: They would soon realize that their intuition was not so unfounded. Alzheimer’s was being investigated in other parts of the world, but no one could foresee that a university hospital in a Colombian city could be so important in the process of understanding the disease.
Our producer David Trujillo will continue the story after a break.
We’ll be back.
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[Daniel]: We’re back with Radio Ambulante. This is David Trujillo.
[David Trujillo]: When Francisco visited his grandmother with Alzheimer’s, he was very surprised by the aggressiveness of the disease and by how quickly it progressed. He was just beginning his medical studies, so he could give only one explanation.
[Francisco]: It seemed to me at that time that this had to do with negligence on the part of . . . of the doctors.
[David]: Actually, at that time it was not medical malpractice, but a lack of knowledge. Francisco was realizing this as he advanced in his studies. That was how he learned, for example, that Alzheimer’s had been registered as a disease for a relatively short time. It was not until 1906 that the German psychiatrist Alois Alzheimer was the first to describe one woman’s particular symptoms: disorientation, incoherent speech, memory loss . . .
When the woman died, Alzheimer was able to examine her brain in detail. He put a small part under the microscope, and when he saw it, he realized something that Francisco also saw at the university:
[Francisco]: You apply a special dye and you can see a spot in the center. It looks yellow. And around the periphery a crown of . . . of black spots.
[David]: Alois Alzheimer was the first person to describe these spots surrounded by crowns—or senile plaques and neurofibrillary tangles, to be more technical—and relate them to a disease that had never been recorded. In 1907, Alzheimer published the full study of his discovery, and three years later the disease began to be known by his name. But it would take decades of research to understand what those spots surrounded by crowns were and what produced them.
When Francisco and Lucía began their research in the 1980s, the rest of the world was just beginning to answer these key questions about Alzheimer’s.
First the basics: those spots are made of poorly processed protein. Francisco calls them “trash.”
[Francisco]: So, it’s two kinds of trash: amyloid in the heart of the plaque.
[David]: In other words, the yellow spot is from a protein called amyloid—beta amyloid, to be exact.
[Francisco]: And tau on the periphery of the plaque.
[David]: The crown of black spots around it is another protein called tau.
But these spots don’t only show up in the brains of people with Alzheimer’s. They also appear in those who do not have the disease.
[Francisco]: Yes, there are plaques in normal aging, but not to a degree that is enough to produce memory loss or loss of higher mental functions.
[David]: in other words, there are many more spots in Alzheimer’s patients and that is what triggers the symptoms.
When Lucía told Francisco about the woman’s case, she also showed him something very important: genealogy. That’s what they did with patients who had this disease: look into their family history to see if there were similar cases. Not to cure it, because even today, there is no way to treat this disease, but if they found a hereditary origin, they could, for one thing, warn the family about future cases. And for another, they could collect valuable information to start studying a possible treatment.
Lucía had begun to study medicine and later became a nurse, but she had always been interested in psychology. Even since 1983, when she went to work in the neurology area of the hospital, she had been accompanying Francisco in all possible patient visits. That is how she had become very familiar with the diagnostic procedures, so in this case she took a pencil and paper and began to talk with the woman’s relatives. It is important to clarify that, as with the first patient, there was an agreement not to reveal her name.
Lucía asked the relatives to tell her how they were related to her, who her ancestors were and their dates of birth. With that information, Lucía began to draw the family tree.
[Lucía]: Genealogy has some special shapes. For example, men are shown as little squares, and women are little circles.
[David]: If two people were a couple, Lucía connected them with a horizontal line . . .
[Lucía]: The children who come from them are shown as squares or circles and all their birth dates are recorded.
[David]: But also, Lucía asked them a key question: who had shown symptoms similar to those of the woman. If she confirmed a case, she would mark it on the family tree.
[Lucía]: When we want to show that someone is sick, I shade their shape in the diagram in black. So, everyone shaded in black has been affected.
[David]: And it was, indeed, a case of hereditary Alzheimer’s. Lucía can’t remember how many people had black shading, but there were many.
[Lucía]: Not only was that person ill, the father had also been ill, the father’s brothers and the great-uncles and great-aunts. The grandmother had also been affected by something very similar and the family didn’t know what it was.
[David]: Francisco was struck by this genealogy. He had seen something similar in the family tree of the first man who came to the hospital. With this second case he began to notice it more clearly. This disease and the way it presents was something that is known as—and here’s where I get technical—as an autosomal dominant inheritance model.
It sounds very complex, but it basically means that the disease showed up equally in both sexes. The children inherited it directly from their parents. And finally, if both parents were healthy, their children were too.
For Francisco, it was easy to spot all this on the family tree, and from there to draw a very important conclusion: There was a dominant gene causing this early-onset Alzheimer’s. In other words, there was a little part of the genetic material of these people that was different—that had a mutation.
But that wasn’t all he could conclude. Based on the fundamental laws of genetics, Francisco calculated the probability that someone in that family would have the disease.
[Francisco]: If neither of my parents has that mutation, my risk is 0%. If one of my parents has that mutation, my risk is 50%. If both parents have that mutation, my risk is 75%.
[David]: One in nine people over the age of 65 may have Alzheimer’s. It’s a high probability, but 99% of cases are sporadic, that is, they did not inherit it. When there is a sick relative, the possibility of having Alzheimer’s doubles, and if there are two, the risk can increase up to seven times.
What was impossible to know from this family tree alone was what that different, mutated gene was and where exactly it was located. For that, they needed another type of studies.
Lucía accepted Francisco’s proposal to find out more and decided to visit the area where the woman came from. Her idea was to expand her family tree and, above all, to take blood samples from each sick person to preserve their DNA, their genetic material. Although they did not have the means to study these samples in any advanced way, they kept them in the hope that one day they would be able to analyze them better, and with that, perhaps, contribute to a more detailed knowledge of the disease.
Lucía visited first the relatives she had already contacted, and they began to connect her with other neighbors who also had the symptoms.
[Lucía]: Wherever I went, I asked if there were other people affected from the same family. They always pointed out: there is one in that house. So, on the next visit I would go to that house. I asked there and then they would send me from one place to the other.
[David]: They all turned out to be relatives, some in degrees further away than others, but they always had some connection. In addition, it was very common to find marriages between relatives.
Lucía’s trips could last up to a week. She organized her schedule very well in order to have the time available. And she did all this without the support of the hospital.
[Lucía]: I used my salary to go to those remote places; other times, I asked Dr. Lopera. He would give me 20 thousand pesos. Right now, it seems like nothing, but there was a lot of money for transportation and food in the town.
[David]: Despite the many responsibilities she had, she always found the time and money to go. She was passionate about the subject.
[Lucía]: I wanted to know what was happening, since there were so many people with such a strange thing—all with the same thing, you know? At that time there were no roads and you had to ride a mule, at least to show them that a professional was interested in them.
[David]: In many of the homes she visited, there were people who had clearly had the disease for years but had never been diagnosed. Lucía explained to the relatives that they were doing a scientific study, that they wanted to know the origin of their malady . . . On several occasions, they gave her the same answer. Francisco, who graduated as a neurologist but continued to work at the hospital, also heard it when he began accompanying her on those visits:
[Francisco]: They believed that a curse had caused the illness in the family.
[Lucía]: To destroy the myths and beliefs, it was necessary to explain what was happening to them.
[Francisco]: And then we stated that we did not believe in the curse, that we believed it was a disease, and that we also believed it was hereditary.
[Lucía]: “That’s why we’re studying it, so that one day,” I told them, “there might be a way to soften the illness, or if we cannot make it go away, at least we might make it milder.”
[Francisco]: There were families that never accepted what we told them, and continued to believe in the curse. Others were relieved to know that, in reality, it wasn’t a curse.
[David]: And the latter agreed to help them so they could continue their research. The moment they agreed, Francisco examined the sick ones, confirmed Alzheimer’s and prescribed some medications to help them sleep or reduce anxiety. Lucía recorded their personal data, the names of their ancestors, the family members with similar symptoms, and took blood samples.
She wrote that information down on paper, and the family tree began to grow.
[Lucía]: First on loose sheets, then on poster board . . . soon the poster board was too small, so my mother made . . . she joined three pieces of Formica, like for desks. And I was doing one by one using a pencil. I tacked them on, and I managed to tack a lot of people onto the genealogy.
[David]: They were able to record several dozen sick people. But the families in that region of the country were traditionally very large—10, 15, even more than 20 children . . . so it was very likely the gene had moved to other places. So Lucía and Francisco started looking for cases in nearby towns—and it wasn’t at all difficult to find them. When people heard they were coming . . .
[Lucía]: They started showing up. They emerged as if they came from under the rocks, and even more so at that time, because they were families that suffered from the usual deficiencies of a neurodegenerative disease.
[David]: They needed professional help. They had cared for their sick, enduring the same difficulties for many years, with the psychological trauma of watching them deteriorate and, in many cases, losing the economic contribution of a person who was in full productive age. The quality of life of these families was very deteriorated, and they often lacked the means to even cope with the situation.
Scientific research is not linear. In fact, research is often being carried out in many different places on the same topics and at the same time, and scientists share their findings with each other through articles published in specialized journals.
That’s how, in 1991, while Francisco and Lucía continued to collect samples, two scientists came up with an important answer to understand Alzheimer’s.
It had to do with those spots on the neurons, the ones that Francisco calls trash. Well, these scientists discovered that the cells of people with the disease showed a mutation in chromosome 21. Remember that number, 21, which is going to be important. That mutation was what caused the spots.
But scientific research, at least ideally, is not a competition to see who gets there first. The objective is to join forces in order to find solutions to different problems. In 1993, Francisco learned that Kenneth Kosik, an American neuroscientist who worked at Harvard University, would be in Bogotá. Kosik was well known for his Alzheimer’s research, and he was going to give a lecture on it. Francisco did not hesitate for a second. He went there to show him what they had done so far. When he finished his talk, he approached him.
Here is Kosik:
[Kenneth Kosik]: You know, when you’re in the Alzheimer’s field, after you give a talk, many people often come up and say, oh, there’s some other thing, you know, my mother has Alzheimer’s, my father. And so, maybe, there was a half a second when I wasn’t sure if this was something that was going to be really super, super interesting.
[David]: Kosik says that after he gives a talk about Alzheimer’s, it is common for people to come up to him and tell him that their mother or father has the disease. When Francisco approached to tell him what he was doing, Kosik didn’t think it was going to be such an interesting thing . . .
[Kenneth]: But another half a second later, he told me about a very large family. And so, we thought there was a gene, but we didn’t know the gene, and I suddenly realized, oh, my gosh: Dr. Lopera is telling me something that is so unique, so special, that I really want to work on that with him.
[David]: But half a second later, when he spoke to him about family and illness, they thought there was a gene, but they didn’t know which one. And he suddenly realized that Dr. Lopera was telling him something so unique, so special, that he really wanted to work with him.
Francisco showed him the enormous genealogy that he had been drawing up with Lucía. With this information, there was a very clear possibility of finding a gene responsible for the disease.
[Francisco]: And he suggested that we could work together to find out if this family had the mutation that had been reported on chromosome 21.
[David]: Of course, they accepted. It was what Francisco and Lucía were looking for from the beginning: technology and resources to enable them to do more detailed studies.
Around that time, one of the families donated a brain from one of their family members when he died. That brain was taken to Kosik’s laboratory in the United States, and when they examined it, they saw that it was full of the typical spots of the disease. They definitely confirmed that he had Alzheimer’s. With that first brain, they started their own neurobank where they would store the different samples, including the blood samples they had been collecting.
Meanwhile, at the university hospital where Francisco and Lucía worked, the research they were doing was already becoming known. Some of their colleagues—doctors, nurses, psychologists—began to set their eyes on the project, and they joined forces to advance not only this specific Alzheimer’s study, but also others related to different neurodegenerative diseases. Around that time, they created the Neuroscience Group of Antioquia. This made it easier to get financial resources from the university.
Dr. Kosik also gave them special software so they could digitize all the information they had. Since it had become easier to organize the data, they decided to go further back into the past of these families to see if they could discover a common origin, a very, very distant relative who brought the disease to that area and ended up passing it on to other generations.
They went to notaries and churches to get information on ancestors. There Lucía discovered something curious:
[Lucía]: On the death certificates, the priests recorded: “So-and-so died on such date and had this disease.” They didn’t use to say “Alzheimer’s;” they said “softening of the brain.”
[David]: When she checked the age of the person, it matched the average lifespan of the patients she knew: between 45 and 51 years, approximately. That was an indication that the person probably had inherited early-onset Alzheimer’s. They began to go further and further back into the genealogy until they got to about 1645.
[Francisco]: And then we discovered that, sure enough, there was indeed a common trunk. That in Antioquia there was a . . . a phenomenon . . . what is referred to as a founding effect. That is, someone brought that gene, planted it here, and it spread throughout the department (province).
[David]: And during two years of studies with Dr. Kosik, in which they analyzed the DNA of these people, they managed to find something that surprised them: Chromosome 21, the one that had been studied by other scientists in the early 1990s, was not related to this specific type of inherited early-onset Alzheimer’s.
[Kenneth]: And that’s when I realized the problem was going to be more complex. So, I brought in another colleague of mine, a woman named Alison Goate, and in collaboration with her, we looked at many more samples and we finally found the gene.
[David]: Kosik says it was then he realized they were dealing with a more complex problem. He asked a colleague named Alison Goate for help to study more DNA samples until, finally, they managed to find the gene with that mutation that produced this peculiar Alzheimer’s in this specific area…
[Kenneth]: There’s one position, one, you know, of all those DNA three billion letters; there’s one small mistake in one of them.
[David]: He says: There is a part in that gene, one in all the three billion letters of DNA—that is, of genetic information—that has one small error. That gene with the mutation was on chromosome 14. And this very tiny alteration made the descendants of that common trunk suffer from this type of Alzheimer’s for generations and generations.
The first thing they did was tell the people who participated in the study about the discovery.
[Francisco]: And it was clear that it was not a curse, but instead a hereditary disease. And that is why it was very important for them to continue to be involved in the research the group was doing, so that one day we could find a way to control the disease.
[David]: It was great news. They had spent approximately a decade collecting data, samples . . . investing money, time, work, and they finally confirmed the suspicions that began with those first genealogies. But at the same time . . .
[Lucía]: It is a two-edged emotion because yes, it is true, they are corroborating what we saw in the genealogy, in the medical evaluations, but what a shame because when it is sporadic you say, well, it’s just this one person and that’s it. But here you know there will always be someone who has that mutation.
[David]: Mutation, or curse . . . for those suffering from the disease, it’s all the same. The technical name they gave it is E280A in Presenilin 1 . . . But Francisco and his team gave it a simpler name, which matches the way people are called in that region of the country.
[Francisco]: The Paisa mutation, which is uniquely from here.
[David]: And it’s important to be clear: So far, that Paisa mutation, which is specifically on chromosome 14, has not been recorded anywhere else in the world. Furthermore, no other population this large has been found with hereditary early-onset Alzheimer’s disease.
In 1996, they published an article about that discovery in Nature, one of the most internationally well-known scientific journals. Five months later, they published another article in the medical journal JAMA, on the clinical characteristics of this very unique type of Alzheimer’s that exists in Colombia.
The research did not stop there. Over time, more volunteers continued to join in to monitor the disease to see how it was progressing in newer generations. The Antioquia Neuroscience Group continued to feed its database with thousands of people from some 25 families in the region who have the disease. People with the Paisa mutation are also registered there, and today there are approximately 1500.
Although a single blood sample suffices to reveal whether someone has the Paisa mutation even before symptoms develop, the Neuroscience Group chose to keep that information confidential. Researchers do have access to it, but they have an ethical duty not to share it with anyone.
They do it to avoid the psychological impact that could cause a person to know that they will lose their memory in about 10 or 20 years. And that a while later they are going to end up bedridden and unable to do anything. Also, although the test is very reliable, there can be human error in the process, and it is a type of information that should not be shared without absolute certainty. The impact of knowing could be very strong, and the Neuroscience Group does not yet have the capacity to provide adequate and permanent emotional support. All these people know is that they have a very high probability of suffering from early-onset Alzheimer’s . . . and so do their siblings and their children and their grandchildren . . .
What the Group has been doing since the early 1990s is to offer support to relatives and caregivers of the sick to help them cope with the situation. Lucía, who ended up doing a Ph.D. in clinical psychology, is in charge of these projects.
[Lucía]: I set up some workshops that I called psychoeducational where they could talk about their sick relatives, the disease, how they felt.
[David]: They also have caregiving workshops.
[Lucía]: Basic nursing care, skin care, position changes, respiratory therapy, wound prevention and—if they have them—wound care, nutrition, how to help the patient move around, how to get them out of bed without the caregiver getting so tired, you know?
[David]: It is a way of giving back for everything they have provided and continue to provide to the research: genealogies, blood samples, the possibility of having their brain scanned, the donation of brains from deceased family members, trips to Medellín, hospitality when they are visited at their home . . .
That commitment they have to the research is in the hopes that one day they will find something to treat the disease, perhaps to delay it, hopefully to cure it—whatever, but something. And although many people may think Alzheimer’s is not so tough on those who suffer from it, since eventually they will forget about it, and because there is no physical pain, there may be moments of lucidity at first, when they get the shock of realization that that they have an incurable disease that is making worse every day.
I can’t imagine how terrifying it must be to grow up knowing there is a large possibility that one day, you will get lost, you will disappear even while you are still there. What will be that last moment that remains in your memory? Where will you live? With whom? Then I think of the other side, of the people around who are witnessing the deterioration. It’s already devastating to see a single person who is close to you get sick—I cannot imagine when there are several, and on top of that, having to take care of them.
I wanted to know more about what the day-to-day life of one of these caregivers meant, and also what the members of those families felt when they learned that there is a very high probability of having the disease. So, I decided to go to Medellín to talk with some of them.
We’ll be back.
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[David]: We’re back with Radio Ambulante. I’m David Trujillo.
Lucía put me in touch with a nurse who works with the Antioquia Neuroscience Group and who has the Paisa mutation in his family tree. His name is Francisco Piedrahíta.
We met at the Group’s headquarters in Medellín. I arrived early that day in late July 2021, and he suggested we go to one of the offices to talk at leisure.
As we walked, he began telling me about his family . . .
[Francisco Piedrahíta]: I come from a . . . from a union of two first cousins. On my father’s side, my grandmother got sick, grandfather got sick, all my father’s siblings got sick, the only one left is him. And on my mother’s side, four have already died, two of them with the disease.
[David]: And his maternal grandfather, who was the brother of his other grandfather, also became ill . . .
In all, Francisco can count about 12 people in his family who he knows have had early-onset Alzheimer’s disease. Although his mother is 63 years old and his father 70, so far, they have not had symptoms.
[Francisco]: The disease has touched the family very closely and has attacked us from all sides. It seems to me, then, almost a miracle that my father and my mother . . . to be with them because I did the math and I should not have either a father or a mother by now, because I said, well, if everyone here is going to get sick, they are going to get sick too.
[David]: But that’s the mutation—sometimes it is inherited, sometimes not . . . Although there is a possibility that it will develop later. You never know.
[Francisco Piedrahíta]: You know, my mother would repeat anything twice and I wanted to die. My father would say I forgot…, I lost the . . . and I’m: Oh no, here we go. Time passed, time passed, time passed. When they turned 55 and up, I began to calm down, because the older you get, the risk of developing the disease decreases.
[David]: He is talking about early-onset Alzheimer’s. If they go over 50 without symptoms, it is more likely that they do not have the mutation.
Francisco is 42 years old and grew up on a farm in the same area north of Medellín. Ever since he can remember, he has had people with Alzheimer’s around, and not only in his family, but also the neighbors . . . with whom he was distantly connected on the family tree.
Francisco remembers seeing them as a child:
[Francisco]: They walked around but they didn’t speak or anything, and then they adopt a position like slouched and stare into your eyes, so you get scared. I remember my little brother crying and screaming because he was very afraid of them. At that time, we did not know what was happening to our loved ones; it was just said, “He became a fool.” “He got foolishness, he got the foolishness,” and that was it. Because the word Alzheimer’s did not exist.
[David]: Well, it didn’t exist for them . . . no one had taught them. No doctor had ever given them a diagnosis. But then, in the mid-80s, Lucía arrived. Francisco was about seven years old.
[Francisco Piedrahíta]: I remember the first time Dr. Lucía arrived. She came to my house and said to my mother, “Hey, tell me something, are there people around here like this, like this, like that,” and ha! My mother starts, “There is one there. Another one over there who died, there another, and there another, and there another, another, another, another, another.” Lucía was stunned, “How so? So many?”
[David]: Yes, many. That’s when Lucía began doing what we talked about: genealogies, taking samples. Some time later, Francisco remembers that doctors from the Antioquia Neuroscience Group went there to explain about the research.
[Francisco Piedrahíta]: They held a meeting for us at the village school and that’s where it became official, they told everyone: this is what you have. It is called such-and-such, it manifests itself in the following way. That was when we all found out.
[David]: Francisco also had blood samples taken at age 14. Then, in 1995, the Paisa mutation was confirmed, on chromosome 14, and they were told that it was very important to continue with the research to find a possible treatment for Alzheimer’s. And although they always made it clear that it would not be soon, it was a light for these families . . . and, in fact, in many cases, that is the only hope they have to perhaps break free from that inheritance.
[Francisco Piedrahíta]: We are eternally grateful to them for that commitment, for that love, for that dedication to finding a solution to the illness we have.
[David]: Francisco studied to be a nursing assistant, and in 2009 Lucía invited him to accompany her to teach the workshops they offer to the relatives of the sick. Since then, he has worked in the Antioquia Neuroscience Group, becoming fully involved in the issue of early-onset Alzheimer’s beyond what he has experienced in his family.
Meeting Francisco had an impact on me. All his life surrounded by this very tough disease, and still he chose to keep on seeing it at all hours, all the time. He explained this to me as follows:
[Francisco Piedrahíta]: It was affecting me a lot because I was getting very sensitive. Actually, I ended up having to do some mental feedback and press ahead. This is my job. And you have to help and collaborate.
[David]: At one point I thought that, after so many years of being so close to the disease, maybe he had gotten used to it, at least in some way. But no.
[Francisco Piedrahíta]: There are times when I think and I say, “It is such a big world and we are the only ones touched by this disease.” One always has that latent fear. There are days when you get up or think about it and say, well, who is next? And now, who is next?
[David]: Now he is approaching 45, and he has cousins of almost the same age who are beginning to show symptoms. And although his parents have not developed the disease, they don’t know whether or not they carry the Paisa mutation. And he doesn’t know, either. And that is perhaps the biggest dilemma a person like Francisco can have. To know or not know.
[Francisco Piedrahíta]: I am not going to start looking for what I haven’t lost. If I have lived 42 years, and to be where I am and to be happy, I don’t need that information, for the rest . . . from now on, I won’t need it, either. So, if I find out, I’m not going to solve or fix anything; I think it’s OK the way it is.
[David]: I must confess that before hearing this answer I thought surely I would want to know without hesitating for a second. I’m one of those people who can cope better with certainty. But then I got Francisco’s point. That information is not going to change anything in practice. It only increases for sure the anxiety of knowing that the inevitable is coming and of always thinking the moment has arrived. And, as he told me, ultimately, he’s not afraid of dealing with the disease as such . . .
[Francisco Piedrahíta]: Because in reality it is a disease that I will forget about and that does not hurt. For me it is scarier to think, who will I go to for care? Who will I be a burden to?
[David]: For many people with the Paisa mutation, or indeed anyone who has the possibility of developing Alzheimer’s, that is their biggest concern. Who would take care of me? Who am I going to be a burden to?
[Gladis Betancur]: Good afternoon . . .
[David]: Hello, Gladis . . .
Francisco suggested that I speak with his cousin, Gladis Betancur. It was her turn to take care of her mother, Magnolia Piedrahíta. The first symptoms began a year after her newborn baby died. Magnolia was only 47 years old. At first, they were things that didn’t seem important . . . for example, she would bring coffee to her husband, and when she returned to the kitchen with an empty cup . . .
[Gladis Betancur]: She was kind of thinking, “Am I . . . am I bringing the cup back or am I going to serve the coffee?” Then she would go again and serve him coffee. “But mom, you’ve already brought my dad coffee.” “Oh, really? Oh, OK.” And a while later, she would do it again.
[David]: She would also say the same thing, over and over . . . When that happened, Gladis, in her ignorance, made her realize.
[Gladis]: “Mom, you already told me.” Then she would lower her head and get sad.
[David]: And it’s because Magnolia had already seen it up close. One of her sisters, for example, had died with Alzheimer’s when she was less than 40 years old, and soon after, her mother, that is, Gladis’ grandmother, got the disease and also died.
[Gladis]: My mother was a person who said, “Oh, may God spare me from it,” because “how scary not knowing where you are.” Like having someone take care of her, or have to help her dress. I mean, she was always very worried about that.
[David]: Although there were moments of denial, there always comes a time when the disease reveals itself.
[Gladis]: For example, we didn’t think my mother was in bad shape until one day she went out naked.
[David]: That day, Gladis was walking toward her mother’s house. From outside, she caught a glimpse of her.
[Gladis]: When I saw her picking up some clothes, that is, we had finished washing them, she went out to get those clothes to put them on. I yelled and said “My God, mom, what are you doing here like this? Come here.” And I got her inside right away.
[David]: At that moment, Gladis understood.
[Gladis]: I started to cry. Seeing her outside naked, poor thing, makes you say, she is very sick.
[David]: And sure enough, when they took her to the Neuroscience Group, they confirmed the diagnosis: early-onset Alzheimer’s . . . very advanced. At the time, Magnolia was only 49 years old.
Gladis was not living with her mother at the time. Even so, she was the one who devoted herself to fully taking care of her. There was no explicit agreement with the rest of the family. But she has always been a great support to her siblings and she is the one who helps them make decisions. So she started going to the Neuroscience Group workshops to learn about basic caregiving and to get psychological support.
There they recommended not touching the subject of the disease in front of Magnolia so as not to affect her emotionally. It’s advice doctors usually give because, although they will surely forget it, it’s better to avoid the emotional blow of the moment. Because of this, Gladis was never able to talk to her about what she was feeling. Still, the deterioration was very fast, and although she could move and do some things on her own, it was increasingly difficult to have a conversation with her.
[Gladis]: In other words, words were not clear anymore. For example, the last thing she stopped calling us was the . . . my youngest sister, she was no longer able to call her “mi niña,” so she called her “mi lila.” And I would say, “What? Who, where is she?” “There, right there.” And I would say, “Who is that?” “It’s Lila.” But she was very confused by then.
[David]: Five years later, her ability to speak definitely deteriorated. Although Gladis is sure that Magnolia sometimes recognized her . . .
[Gladis]: When I got home, she made a gesture as if showing she was happy. And that was all. And that . . . whoa, super-hard, super-hard. In other words, you don’t know what could be going through their head. Sometimes tears came to her eyes and you didn’t know why.
[David]: Other times, she got very aggressive. She would yell, hit people, damage things, wouldn’t stay still . . . The area of the brain where protein spots start to appear also has to do with emotions. For this reason, Alzheimer’s patients have these symptoms of emotional instability.
[Gladis]: I tried my best, but sometimes you also get impatient. You want to run because you think “God, what am I going to do?” I mean, sometimes I literally sat down to cry.
[David]: Gladis also had to deal with her dad becoming addicted to alcohol and drugs. To make things easier, she decided to move her mother over to her house. Since she had to take care of her most of the time, she had to stop working. The financial situation became critical. In addition to household expenses, Gladis had to pay for transportation to run errands for her mother, get the medications, request medical exams. And, of course, Magnolia needed special things: food supplements, diapers . . .
[Gladis]: In the middle of all that, the father of my daughters also decided to leave the house. Twenty years of marriage ended because of that situation. You know that you have to leave everything aside because there is that sick person there who is the one who . . . who requires all of your time.
[David]: Not all the siblings helped her, and those who did, did it at specific times and for short periods. Nor did they give much money and it was not constant, so Gladis’ oldest daughter, who was 16 years old and the one who helped the most with Magnolia’s care, decided to start working to contribute financially.
Gladis’ social circle shrank. And not just because she no longer had time to go out, but because people stopped looking her up. Her friends drifted away, even her extended family.
[Gladis]: People make excuses every day: Oh, I don’t visit because I don’t like to see her like that. Others: Oh, no, the issue is that she yells a lot, so, no way. But not even a call for my own sake: How are you? How is your mother? I mean, no. They completely drifted away.
[David]: She mentions only a few people who were with her the entire time. Among these is her cousin Francisco, the nurse from the Neuroscience Group.
Some time later, Magnolia had a very strong seizure. This can happen in some patients with advanced Alzheimer’s, and in her case, it took away her mobility and put her in bed permanently. She couldn’t even eat by herself anymore.
Gladis’ responsibilities increased. Now she had to do absolutely everything for her mother. There were moments of impatience, despair, and helplessness, but despite the deterioration . . .
[Gladis]: You always live with the hope they will somehow get better, even though it is deep down, you always think, well, maybe . . .
[David]: Maybe if I make an effort, maybe if I take better care of her, maybe if I try to talk to her, maybe if I help her hold on a little longer until science finds a way . . . But those hopes didn’t last long.
[Gladis]: Knowing that she is there but that she is not there. In other words, what quality of life does such a person have? Whether she has pain, that is, she does not know how to tell you where it hurts. I mean, it’s like, like a baby.
[David]: In 2017, at age 60, Magnolia fell ill with pneumonia. As Gladis recalls, she did not complain of any pain. They only found out how serious it was because of the high fever and the results of the tests they were doing. She was already very deteriorated, so her doctor preferred to give her all the necessary medicines and care at home. But she didn’t last long. She died within days, having lived more than a decade with diagnosed Alzheimer’s.
Gladis is 42 years old and so far, she has had no symptoms of the disease. She is still closely linked to the Antioquia Neuroscience Group. Since 2013, she has volunteered in a clinical trial that includes 252 people who might have the mutation. Among those is also the mother of Francisco, the nurse. And, as often happens in these human studies, some of the people have been given a placebo. The others received an experimental molecule that, if it works, may help treat the disease. They expect the final results of the study to come out in 2022.
Finally, how does it feel to live with that permanent fear of . . . thinking there is something there?
[Gladis]: Well . . . how can I tell you—I try, I try to . . . not give it importance, but sure, there is always some fear. And especially with my daughters. If I don’t get it, they will be spared. If I get it, you say to yourself, I know there is a chance they will be next.
[David]: And since Tatiana, her oldest daughter, was there, I asked her the same question . . .
[Tatiana Rojo]: Well, let’s say that at that moment I am not afraid. There is a reason why the Neuroscience research has lasted so long. I think that if it had not worked at all, they would have ended it long ago.
[David]: In fact, since 2015 they have been studying a case that could be the most important in these 30 years of research. At that moment they discovered a woman in their database named Aliria Piedrahíta. Although she was 72 years old and carried the Paisa mutation, she had not developed symptoms of the disease.
When they did detailed studies on her at a hospital in Boston, they discovered that she had another mutation that prevented the formation of too much tau, the trash that forms the black crowns around the spots or senile plaques. That made her have no symptoms of the disease. In a few words, Aliria’s biology could be the answer to finding the cure for Alzheimer’s, and not just this hereditary and early-onset type.
In 2019, Dr. Francisco Lopera and his colleagues published Aliria’s case in the journal Nature. A year later, Aliria died of cancer when she was about to turn 78 and symptoms had just started. But her contribution to this research did not end there. Her family donated her brain so that scientists could continue studying it and understand how it worked. If they can mimic what that brain did in a person with Alzheimer’s, they could delay symptoms or make them less severe.
Francisco, who is 70 years old at the moment, does not dare to say how long results from Aliria’s brain analysis would take. He insists that he will remain involved in the research for as long as he can. And even when he’s gone, other people are going to continue it. If they manage to find a cure for Alzheimer’s one day, Francisco will have fulfilled that promise he made when he was just beginning to study medicine more than 50 years ago—that no grandmother would stop recognizing her own children.
[Daniel Alarcón]: The Neuroscience Group of Antioquia continues to search for other people who have the same particularity as Aliria, and not only in that region. They also investigate other neurodegenerative diseases.
If you live in Colombia and have a relative with Alzheimer’s, you can contact the Antioquia Neuroscience Group and enroll them in the Alzheimer’s Prevention Plan program. If you want more information, we have put a link in the description of the episode.
David Trujillo is a producer for Radio Ambulante. He lives in Bogotá. Thanks to our producer Lisette Arévalo for interviewing Dr. Kenneth Kosik and giving more strength to this episode.
This story was edited by Camila Segura and me. Desirée Yépez did the fact-checking. The sound design is by Andrés Azpiri and Rémy Lozano, with original music by Rémy.
The rest of the Radio Ambulante team includes Paola Alean, Nicolás Alonso, Xochitl Fabián, Fernanda Guzmán, Camilo Jiménez Santofimio, Ana Pais, Laura Rojas Aponte, Barbara Sawhill, Elsa Liliana Ulloa and Luis Fernando Vargas.
Emilia Erbetta is our editorial intern.
Carolina Guerrero is the CEO.
Radio Ambulante is a podcast by Radio Ambulante Estudios, produced and mixed on the Hindenburg PRO program.
Radio Ambulante tells the stories of Latin America. I’m Daniel Alarcón. Thanks for listening.
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