<The paisa mutation

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Let's start at the San Vicente de Medellín University Hospital.It is one984 and Francisco Lopera, a last year student of neurology, is doing the routine: receive and register the patients who arrive.

Francisco Lopera: Then there were a patient in the emergency room.The family brought him because he had lost his memory and was changing behavior and could no longer work, because he was a farmer.He embomed to go to ... he milked her cows or go to do the field activities.So I decided to hospitalize it to make checks.

Alarcón: Francisco did some neuropsychological tests: memory evaluations, attention, concentration and even mathematical reasoning tests.From before studying medicine, the brain, its functioning and the diseases that attacked it had fascinated him.

Lopera: What interested me was dementia, language problems, attention and concentration problems, reasoning problems, memory problems.

Alarcón: So I wanted to understand how this patient's brain was handling memories.

Lopera: When we evaluated it, I discovered that this patient had a memory disorder very similar to what was described in patients with Alzheimer's.

Alarcón: Francisco had already studied Alzheimer.Which usually appears with old age, when spots are forming in the brain area related to memory.That in some cases it appears sporadically ... but that in others can inherit.That at first some mild symptoms appear, such as spatial confusion, sudden forgetfulness or repetition of questions.

That the disease does not kill those who suffer from it, but in the 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 that has no cure.

And, well, in addition to knowing the theory, he had also seen him closely: his grandmother suffered from Alzheimer's when he was about one9 years old and began studying medicine.It was sporadic, that is, there was no family history.They had taken her where several specialists and nothing could be done.Very fast stopped recognizing his children.

Lopera: And I was then the promise that when I was a doctor that was not going to happen to any grandmother, that they did not recognize their children.

Alarcón: That's why he was so interested in this patient.The results of the exams clearly pointed to Alzheimer's ...

Lopera: But the only thing that I didn't fit was that I was very young: the patient was 47 years old.Normally Alzheimer begins after 65 years.

Alarcón: And he had never seen that.Francisco investigated more and found something that intrigued it: in the world some cases of young people with Alzheimer had been recorded, but it was not known what produced it.Talking to the patient's family, he learned that both his mother, and one of his grandparents, began to lose their memory as young as he.Although they never diagnosed them, they died with very similar symptoms.

The diagnosis reached Francisco and his colleagues was an alzheimer -inheritant -on -pegz dementia.But they couldn't do anything else: they sent him back home with recommendations to take care of him.Since Alzheimer's has no cure, the only thing doctors can do is prescribe something to sleep, 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.I wanted to look for more answers.But at that time, he couldn't do much more to solve the mystery.He was just a student and had how to do more detailed exams of the brain.

He only collected all possible data on symptoms, context in which they lived, ages and, some time later, with an agreement not to reveal names, wrote a scientific article together with Atres other colleagues that involved in the same hospital to record the strange case.

Soon to meet that first patient, the story was repeated: a woman arrived at the hospital with similar symptoms.This time a nurse received her, Lucía Madrigal ...

Lucia Madrigal: a patient in the 40s who had...Well, he was rare.That had changed.The family said that he did not remember anyone and that he remembered a lot of the old and the new did not remember it.

Alarcón: It came from a town in the same area north of Medellín where he was the first man who had obsessed Francisco.Lucia already knew that case, and the next day he told Francisco.The woman seemed to have Alzheimer's and, like the other patient, she was also early.It was too coincidence that these very rare conditions were just in two people from the same area.

Madrigal: I asked what we can do.And he told me no, because we have no way of working.We would have to have projects to be able to do it, money...

Alarcón: Francisco was intrigued, but it seemed like a risky bet.At that time, the mid -80s, it was not very good why Alzheimer.As in the first case, they also had no resources to investigate thoroughly: they could not do detailed studies of the brain or analyze the DNA, but their intuition pointed to the fact that in the brains of those people there were valuable answers to better understand Alzheimer's.Francisco asked him if he was interested:

Madrigal: And I was pulling the thread of the data they had given me and I started working.

Alarcón: They would soon realize that this intuition they had was not so unfounded.Alzheimer.

After the pause, our producer David Trujillo continues to tell us ...

We'll be back.

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Alarcón: We are back on Radio Ambulante.Here David Trujillo.

David Trujillo: When Francisco visited his grandmother with Alzheimer's, he was very surprised by the aggressiveness of the disease and the speed with which he advanced.He was barely starting to study medicine, so he could only give an explanation.

Lopera: It seemed to me at that time that this was negligence of the ... of the doctors.

Trujillo: Actually, at that time it was not about medical negligence, but of ignorance.Francisco was understanding him as he advanced in his career.Thus he knew, for example, that Alzheimer's was a disease registered for a short time.Only in one906 the German psychiatrist Alois Alzheimer's first described the particular symptoms of a woman: disorientation, incoherence when speaking, memory loss ...

When the woman died, Alzheimer could examine her brain in detail.He put a part in the microscope and when he saw her realized something that Francisco also saw in the university:

Lopera: You make a special coloration and you can see a stain in the center.Yellow.And on the periphery a crown of ... of black spots.

Trujillo: Alois Alzheimer was the first person to describe these spots surrounded by crowns -o.In one907, Alzheimer published the full study of his discovery, and three years later they began calling that disease with his name.But decades of research would pass to understand what those spots were surrounded by crownsy what produced them.

When Francisco and Lucia began his research, in the 80s, in the rest of the world these key questions about Alzheimer's were just beginning to answer.First the most basic: those spots are made of poorly processed proteins.Francisco calls them "garbage".

Lopera: Then there are two garbage: amyloid in the heart of the plate.

Trujillo: that is, the yellow spot is of a protein called amyloid ... beta amiloid, to be exact.

Lopera: and tau on the periphery of the plate.

Trujillo: The crown of black spots around is from another protein called Tau.But these spots are not only in the brains of people with Alzheimer's.They also appear in those who do not have the disease.

Lopera: there are plaques in normal aging, but in such a degree, that it fails to produce loss of memory and loss of higher mental functions.

Trujillo: that is, there are many more spots in patients with Alzheimer's and that is what unleashes the symptoms.

When Lucia told Francisco the case of the woman, she also showed her something very important: the genealogy.That was what they used to do with patients with this disease: find out in their family history if there were similar cases.Not to cure it, because still, today, there is nothing to treat this disease, but if they found a hereditary origin, they could, on the one hand, warn the family about future cases.And on the other, collect valuable information to start studying a possible treatment.

Lucia had begun to study medicine and then dedicated himself to nursing, but psychology always interested her.Since one983, when he entered the hospital neurology area, he had been accompanying Francisco in all possible consultations.That way I had learned the diagnostic procedures very well, so in this case he grabbed pencil, paper and began talking to the women's relatives.It is important to clarify that, as in the first patient, there was an agreement not to reveal his name.

Lucia asked the relatives to tell her kinship with her, to tell her who her ancestors and the birth dates were.With that information Lucia began to draw the tree.

Madrigal: Genealogy has some special forms.For example: men are squares, women are balls.

Trujillo: If two people were a couple, Lucia connected them with a horizontal line ...

Madrigal: The children, which remain square or balls and all are placed from birth dates, are still...

Trujillo: But also, Lucia asked them a key question: who had symptoms similar to those of women.If they confirmed a case, he pointed it out in the tree.

Madrigal: When we want to show that they are sick, the patient is shaded, he is given a black shadow.So, all those who have black shadow have been affected.

Trujillo: And indeed: it was a case of hereditary Alzheimer's.Lucia does not remember how many people had black shadow, but there were many.

Madrigal: In addition to that person was sick, dad, dad's brothers and uncles and aunts grandmothers had also been.Grandma had also been affected by something very similar that the family did not know what it was.

Trujillo: Franciscole caught this genealogy.I had seen something similar in the tree of the first man who arrived at the hospital.With this second case I began to notice it more clearly: this disease and the way it is presented was something that is known as - and here I get technical - a dominant autosomal inheritance model.

Sounds very complex, but basically it means that the disease was given equally in any sex.That parents were inherited directly to the children.And finally, if both parents were healthy, their children too.

For Francisco it was easy to see all this in the family tree, and hence drawing a very important conclusion: that there was a dominant gene that caused this early Alzheimer.That is, there was a part in the genetic material of these people that was different...that had a mutation.

But that was not all that could conclude.Based on the fundamental laws of genetics, Francisco calculated the probability that someone in that family had the disease:

Lopera: If none of my parents have 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%.

Trujillo: One in nine people over 65 can have Alzheimer's.It is 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.

What was impossible only with this family tree was to know what that different gene, mutated, and where was exactly.For that they needed other types of studies.

Lucía accepted Francisco's proposal to find out more and decided to travel to the area where the woman came.The idea was to expand its family tree and, above all, take blood samples from each sick person to keep their DNA, their genetic material.Although they did not have how to study these samples in an advanced way, they were kept in the hope that one day they could analyze them better, and with that, perhaps, to contribute to a more detailed knowledge of the disease.

Lucía arrived first where the relatives who had already contacted, and they began to connect with other neighbors who also had the symptoms.

Madrigal: where we arrived we asked if there were more affected people from that same family.They were always pointing to us: in that house there is a.So, to the next visit I went to that house.I asked there and then I was moving from one part to the other.

Trujillo: Everyone turned out to be familiar, some in degrees farther than others, but they always had some connection.In addition, it was very common to find marriages in relatives.

Lucia's trips could last up to a week.I organized its schedules very well to have the time available.And all this did without support from the hospital.

Madrigal: I went to the sidewalks with my salary, other times because I asked Dr. Lopera.He gave me 20 thousand pesos.Right now it seems nothing, but it was a lot of money for transport, to eat in the town.

Trujillo: Despite the many responsibilities he had, he always got time and silver to travel.I was passionate about the subject.

Madrigal: I wanted to know what was happening, that there were as many people as with a strange thing ... all with the same, right?At that time there were no roads, it was a mule loin that we had to go, at least to see a professional who was being interested in them, right?

Trujillo: In many of the houses I visited, there were people who clearly had the disease for years but had never been diagnosed.Lucia explained to the relatives that they were doing a scientific investigation, who wanted to know the origin of what they suffered ... on several occasions they gave him the same answer.Francisco, who graduated as a neurologist but continued working at the hospital, also heard her when she began to accompany her to those visits:

Lopera: they believed there was a curse that produced the disease in the family.

Madrigal: To break the myths and beliefs, it was necessary to explain what happens.

Lopera: And then we stated that we did not believe in the curse, that we believed was in a disease, and that we also believed it was hereditary.

Madrigal: That's why we are studying it, so that one day, I told them, there is something that this disease can be alleviated, or that you can not remove, at least make it softer, right?

Lopera: There were families who never accepted what we told them and kept believing in the curse.Others rested, rested from knowing that not really, it wasn't a curse.

Trujillo: and the latter agreed to help them so that they could move forward with the investigation.At the time they agreed, Francisco examined sick people, confirmed the Alzheimer's and prescribed some sleeping medications well or reducing anxiety.Lucía registered their personal data, names of the ancestors, relatives with similar symptoms and took blood samples.He wrote that paper information, and the family tree began to grow.

Madrigal: First in hojitas, then on cardboard...I was small, then my mother did...It united three tables that are formal from those of desktops.And there I was doing one after another, right?I was hitting them, and I managed to hit a lot of individuals in genealogy.

Trujillo: They managed to register several dozens of sick people.But families in that region of the country were traditionally very large: one0, one5, up to more than 20 children ... That is why it was very likely that the gene would have moved to other places.So Lucía and Francisco began looking for cases in nearby villages ... and it was not difficult to find them at all.When people learned that they arrived ...

Madrigal: They were already appearing.They go out like under the stones, and at that time, with greater reason, because they were families that suffered the usual deficiencies of a neurodegenerative disease.

Trujillo: They needed professionals.They had been with the same difficulties in caring for their patients, with psychological traumas to see them deteriorate and, in many cases, lose the economic contribution of a person who was in full productive age.The quality of life of these families was very deteriorated, and many times they had no tools to cope with the situation.

Scientific research is not linear.In fact, in many places and at the same time, research on the same topics is carried out, and scientists share their discoveries with each other with articles published in specialized magazines.

Therefore, in one99one, while Francisco and Lucía continued to collect samples, two scientists found an important response to understand Alzheimer's.

It had to do with those spots on neurons ... those that Francisco calls garbage.Well, these scientists discovered that in people's cells with the disease there was a mutation within chromosome 2one.Remember that number, 2one, which will be important.That mutation was the one that caused these spots.

But scientific research is not, or at least ideally, a competence of who arrives first.The objective is to join efforts to find solutions to different problems.In one993, Francisco knew that Kenneth Kosik, an American neuroscientist who worked at Harvard University, would go to Bogotá.Kosik was very recognized for his investigations from Alzheimer's, and he was going to give a conference about it.Francisco did not hesitate a second and traveled there to show him what they had done so far.When the talk ended, he approached him.

This is Kosik ...

Kenneth Kosik: You Know, When You're in the Alzheimer Field, After You Give A Talk, Many People Offen Up and Say, Oh, There's Sub Else, You Know, My Mother Has Alzheimer's, My Father.And so for maybe there a ha Half a Second When I was't Sure If This was submiss.

Trujillo: Kosik says it is common that after giving talks about Alzheimer's, people are approaching to tell him that his mother or dad has the disease.When Francisco approached him to tell him what he was doing, Kosik didn't think he was going to be something so interesting ...

Kosik: Buther Half A Second Later, HE TOLED ME BUTT TO VERY LARGE FAMILY.And so we thought there was a gene, but we didn't know the gene, and it suddenly i realized, oh, my gosh: dr.Lopera Is Telling Me Subgoing That is So Unique, So Special, That I Really Want To Work On That With Him.

Trujillo: but half a second later, when he talked about the family and the disease thought there was a gene, but they didn't know which.And suddenly he 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 he had been doing with Lucía.With that information the possibility of finding a gene responsible for the disease was very clear.

Lopera: And he proposed that we could work together to find if this family had that mutation that had been reported on chromosome 2one.

Trujillo: Of course they accepted.It was what Francisco and Lucía were looking for from the beginning: technology and resources to be able to do more detailed studies.

At that time, one of the families donated a brain of one of their patients when he died.That brain took it to the Kosik laboratory in the United States and when they reviewed it they were full of the typical spots of the disease.They definitely confirmed that it was Alzheimer's.With that first brain they opened their own neurobanco where they would store the different samples, including those of blood they had been collecting.

Meanwhile, at the University Hospital where Francisco worked and Lucia was already knowing the research they advanced.Some of his classmates - medical nurses, psychologists - began to put their eyes on the project, and joined to advance not only in that specific study of Alzheimer's, but with others related to different neurodegenerative diseases.At that time they created the neuroscience group of Antioquia.It was easier to receive economic resources from the University.

Dr. Kosik also gave them special software to digitize all the information they had.As it had become easier to organize the data, they decided to go further back in the past of these families and try to discover if there was a common origin, a very distant relative that took the disease to that area and ended up passing it to other generations.

They went to notaries and churches to search for ancestors information.And there Lucia discovered something curious:

Madrigal: In the death games the priests placed: Fulanito died on that date and had this disease.Formerly they said Alzheimer's, they said cerebral softening.

Trujillo: When he reviewed the age of the person, he agreed with the average life of the patients he knew: between 45 and 5one years, approximately.That was an indication that he had probably had a hereditary early Alzheimer's.They began to go further and further back in genealogy until they reached more or less one645.

Lopera: And then we discover that yes, that it was truly a common trunk.That in Antioquia there was a ... a phenomenon ... what is called a founding effect.That is, someone brought that gene, sowed it here, and went back throughout the department.

Trujillo: And in two years of studies with Dr. Kosik in which they analyzed the DNA of these people, they managed to find something that surprised them: that chromosome 2one, the one that the other scientists had studied in the early 90s, was notRelated to this specific type of hereditary Alzheimer's.

Kosik: and that's when i realized that the problems was Going to Be More Complex.So i Broucht in Another Colleague of Mine, to Woman Named Alison Goate.In collaboration with her, we look at many more samples and we finally found the gene.

Trujillo: Kosik says that he realized that they were dealing with a more complex problem.He asked for help from a colleague called Alison Goate, to study more DNA samples until, finally, they managed to find the gene with that mutation produced by that peculiar Alzheimer's in this specific area ...

Kosik: There's One Position, One, You Know, Of Those All That DNA, Three Billion Letters, There's One Small Mistake In One of Them.

Trujillo: says: there is a part in that gene, one throughout the DNA of three billion letters, that is, of genetic information, which has a small mistake.That gene with the mutation was on chromosome one4.And this very tiny alteration, lowercase, made the descendants of that common trunk carry generations and generations suffering from this type of Alzheimer's.

The first thing they did was tell the discovery of the people who participated in the study.

Lopera: And it was clear that it was not a curse, but that it was a hereditary disease and that was why it was very important that they were still linked to the investigations that the group was doing, so that one day we could find a way ofcontrol the disease.

Trujillo: It was great news.Approximately one decade had passed data, samples ... investing money, time, work, and finally confirmed the suspicions that began with those first genealogies.But at the same time...

Madrigal: It is an ambivalence because yes, it is true, they are corroborating what we saw in genealogy, in medical evaluations, but what to weigh, because when it is sporadic one says good, then, it is that it is this person and there is no more.But here one knows that yes, there will always be someone who has that mutation, right?

Trujillo: mutation or curse ... for those who suffer from the disease becomes the same.The technical name they gave him is E280A in Presenilina one ... but Francisco and his team put another simplest name, which coincides with the way they are told the people of that region of the country.

Lopera: the paisa mutation, which is unique here.

Trujillo: And it is important to make it clear: so far, that paisa mutation, which is specifically on chromosome one4, has not been recorded anywhere else in the world.Moreover, no other population has been found with a hereditary premature Alzheimer's.

In one996, they published an article about that discovery in Nature, one of the most internationally recognized scientific journals.Five months later, they published another article in the JAMA Medical Magazine, about the clinical characteristics that this type of Alzheimer's so particular has in Colombia.

The investigation did not stop there.Over time they continued to join more volunteers to monitor the disease and know how it was advancing in new generations.The neuroscience group of Antioquia continued to feed its database with thousands of people from about 25 families in the region who have the disease.There are also registered people who have paisa mutation, and today are approximately one.500.

Although only with a blood sample it can be revealed if someone has the paisa mutation even before developing symptoms, the neuroscience group chose to maintain the confidentiality of that information.Researchers do have access to it, but they have the ethical duty of not sharing it with anyone.They do it to avoid the psychological impact that could cause a person to know that in about one0 or 20 years he will lose his memory.And that in a while, he will end up prostrated in a bed without being able to do anything.In addition, although the test is very reliable, there may be human errors in the process, and it is a type of information that should not be shared if there is no absolute certainty.The impact of knowing that could be very strong, and the group of neurosciences does not yet have the ability to provide adequate and permanent emotional help.The only thing these people know is that they have very high chances of suffering early Alzheimer's ... and also their brothers and their children and their grandchildren ...

What the group has been doing since the early 90s is to offer support to relatives and caregivers of the patients to be able to cope with the situation.Lucía, who ended up doing a doctorate in clinical psychology, takes care of those projects.

Madrigal: I set up some workshops that I called them psychoeducational so that they could talk about the patient, about the disease, how they felt.

Trujillo: They also give care workshops.

Madrigal: Basic nursing care, skin care, position changes, respiratory therapy, wound prevention and, if they are careful, nutrition, how to mobilize the patient, how to get off the bed without the caregiver beingTired so much, right?

Trujillo: It is a way to give back everything they have given them and continue giving the investigation: genealogies, blood samples, the possibility of scanning their head, the donation of the brains of family members who die, trips to Medellín,Hospitality when they visit them in their homes ...

That commitment they have with research is for the desire to find something to treat the disease, maybe to delay it, hopefully to cure it ... whatever, but something.And although for many people the Alzheimer's do not seem so hard for those who suffer from it, because it will finally be forgotten, because there is no physical pain, at first there may be moments of lucidity in which they collide with the revelation of sufferingan incurable disease, which every day puts them worse.

I do not imagine how terrifying it should be to grow knowing that there is a big possibility that one day you get lost, that you will disappear even being there ... What will be the last moment that is left in memory?Where will you live?With who?Then I think of that other side, on the people around who are seeing the deterioration: if it is already devastating to see that a single close person is sick, I do not imagine when they are several and also have to take care of them.

I wanted to know with more details what the day -to -day life of one of these substances meant and also what the members of these families felt when there is a very high probability of having the disease.So I decided to uviajar Medellín to talk to some of them.

We'll be back.

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Trujillo: We are back on Radio Ambulante, I'm David Trujillo.

Lucia contacted a nurse who works in the neuroscience group of Antioquia and who in her family tree has the paisa mutation.His name is Francisco Piedrahita.

We are at the group's headquarters in Medellín.I arrived early that day, at the end of July 202one, and he told me to go to one of the offices to talk calmly.While we walked, he started talking to me about his family ...

Francisco Piedrahita: I come from one ... from a union of two cousins, on the side of my dad, the grandmother got sick, the grandfather became ill, all my dad's brothers became ill, the only one left is him is him.And on my mother's side, four have already died, two with the disease.

Trujillo: And his maternal grandfather, who was the brother of his other grandfather, also got sick ...

In total, Francisco manages to count about one2 people from his family who knows that they have had an early Alzheimer's.Although his mother is 63 years old and his dad 70, so far they have not had symptoms.

Piedrahita: The disease has touched the family very closely and has attacked us on all sides.It seems to me, then, almost a miracle that my dad and my mother...Be with them because I did the account and I, for these times, I would not have a dad or mom, because I said, well, if here everyone is going to get sick they will also get sick.

Trujillo: But this is the mutation: sometimes it is inherited, sometimes not ... although it is possible to develop later.You never know.

Piedrahita: No, my mother repeated anything and I wanted to die.My dad said I forgot ..., it was lost ... and I oh, it's going to start.Time was spending time, time spending time.When they started as more or less than 55 years up, I was reassuring myself, because the greater the risk of developing the disease is decreasing.

Trujillo: Refers to this early Alzheimer's.

Francisco is 42 years old and grew on a farm in the same area north of Medellín.Since he has reason he has had Alzheimer's patients around, and not only in his family, also the neighbors ... with whom he was finally connected in the family tree.

Francisco remembers seeing them as a child ...

Piedrahita: they walked around but they didn't speak anything, and as they are adopting a position like agacaditos and look at a fixed eye then one scared.I remember that my little brother cried and shouted because it was very afraid.We did not know what was happening with our loved ones at that time, it was simply said "he embostered"."He gave him the buble, gave him the buble" and is already.Because the word Alzheimer did not exist.

Trujillo: Well, it didn't exist for them ... nobody had taught them.No doctor had given them a diagnosis.But then, in the mid -80s, Lucia arrived.Francisco was about seven years old.

Piedrahita: I remember the first time the Dr. Lucía arrived.She arrived at my house and told my mother: you hear, tell me one thing, here there are people like that, so, and ha!My mother begins: See, in such part there is a.There another one died, there another, and there another, and there another, another, another, another, another.Lucia was stunned, how?So many?

Trujillo: Yes, many.There Lucia began to do what we already have: the genealogies, the samples..Some time later, Francisco remembers that they were doctors from the Antioquia Neurosciences Group to explain the research.

Piedrahita: They made us a meeting at the Veredal School and that was where he became official, everyone was told: this is what you have.It is called that, it's called Asá, it manifests itself as follows.That's where we all find out.

Trujillo: Francisco also took blood samples at age one4.Then, in one995, it was when they confirmed the Paisa mutation, on chromosome one4, and they were told that it was very important to continue the investigation to find a possible treatment of 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 break that inheritance with that inheritance.

Piedrahita: We live eternally grateful to them for that commitment, for that love, for that dedication in looking for a solution for this disease of us.

Trujillo: Francisco studied to be a nursing assistant, and in 2009 Lucia invited him to find her the workshops offered to the relatives of the patients.Since then he works in the neuroscience group of Antioquia, getting fully involved in the theme of early Alzheimer's beyond what he has lived in his family.

Meet Francisco impacted me.All his life surrounded by this hardness so hard and still choose to continue seeing it at all hours, at every moment.He explained it to me like this:

Piedrahita: I was affecting me a lot because I was getting very sensitive.I really had to make mental feedback and continue.This is my job.And you have to help and collaborate.

Trujillo: At one point I thought that after so many years of being so close to the disease, he had accustomed himself to her ... thus out of a certain way.But not.

Piedrahita: Sometimes I think and I say but such a big world and touching us only with this disease.One is always like that latent fear.There are days that one gets up or thinks about that and says, well, and now who follows?And now who is still?

Trujillo: Now he is approaching his 45 years, and already has cousins of almost the same age to those who are starting the symptoms.And although their parents have not developed the disease, they do not know whether or not they have the paisa mutation.And he doesn't know either.And that is perhaps the greatest dilemma that a person like Francisco can have.Know or not know.

Piedrahita: I'm not going to look for what has not been lost to me.If I have been happy for 42 years and where I am I do not need that information, for the others ... what I lack from now on, I will not need it either.So with knowing I will not solve or fix anything, I think that is fine.

Trujillo: I confess that before listening to this answer I thought so, that I would like to know without hesitation a second.I am one of those who live better with certainties.But then I understood Francisco's point: that information will not change anything in practice.Surely it only increases the anguish of knowing that the inevitable comes and always being thinking that the time has come.And, as he told me, ultimately, the disease as such is not afraid to suffer from it ...

Piedrahita: because it is really a disease that I forget and does not hurt.For me it is more fearful to think is, who am I going to get to lead?Who am I going to be a burden?

Trujillo: For many people who have the Paisa mutation, or in reality to anyone who has the possibility of developing Alzheimer's, that is their greatest concern.Who would take care of me?Who am I going to be a burden?

Gladis Betancur: Good afternoon...

Trujillo: Hi, Gladis...

Francisco recommended me to talk to his cousin, Gladis Betancur.She had to take care of her mother, Magnolia Piedrahita.A year after his newborn baby died, the first symptoms began.Magnolia was only 47 years old.At first they were things that seemed small ... for example, it took coffee to the husband and when he returned to the kitchen with the empty cup ...

Betancur: As I said, do I carry the well or will I serve the red?Then she went again and served red.Love, but you already took my dad red.Oh yeah?Oh ok.And the momentary returned and did it.

Trujillo: He also told the same, again and again ... When that happened, Gladis, in his ignorance, made her account.

Betancur: ma, he already told me.Then she crouched her head and became sad.

Trujillo: And Magnolia had already seen him closely: one of his sisters, for example, had died with Alzheimer's with less than 40, and soon to his mother, that is, Gladis's grandmother, the disease beganAnd he also died.

Betancur: My mom was one of those who said "Oh, God allows me not to give me why one without knowing where it is standing".Like they had to take care of her, as if they had her until putting the clothes.I mean, she lived as very worried about that.

Trujillo: Although there were moments of denial, the time always comes when the disease is revealed.

Betancur: For example, we don't think my mother was so bad until one day she got naked.

Trujillo: That day, Gladis was walking towards her mother's house.From outside it was enough to see.

Betancur: When I saw her taking a clothes, that is, we had finished her, she went out to take that clothes to put it on.I hit him was the cry and I “love, but for God's, what are you doing here?Come on".And right there then I entered her.

Trujillo: At that time, Gladis understood.

Betancur: I started crying.One and see her naked outside one already says: it is very bad.

Trujillo: And indeed.When they took her to the neuroscience group confirmed the diagnosis: early Alzheimer's ... very advanced.For that moment, Magnolia was only 49 years old.

Gladis did not live with her mother at that time.Even so, she was the one who devoted himself to caring for almost completely.There was no explicit agreement with the rest of the family.But she has always been great support for her brothers and is the one who helps them make decisions.So he began to go to the workshops of the neuroscience group to learn about basic care and have psychological support.

There they recommended not touching the issue of the disease to Magnolia so as not to affect it emotionally.It is an indication that doctors usually give because, although they will surely be forgotten, it is better to avoid the emotional blow of the moment.Therefore, Gladis could never talk to her about what she felt.The same, the deterioration was very fast, and although he could move and do some things alone, it was increasingly difficult to hold a conversation with her.

Betancur: that is, the word was not clear.For example, she the last thing she stopped ... to tell us went to the ... to my little sister the child, who was no longer able to tell her my girl, then my lilac said.And what happened?Who, where is she?Candle, candle.And I, who is that?The lilac.But already very tightened.

Trujillo: Five years later, his speech capacity deteriorated definitively.Although Gladis is sure that sometimes Magnolia recognized her ...

Betancur: Like I arrived and she did as the gesture that she was glad.And that's it.And that ... uff, super hard, super hard.That is, one does not know what can go through them.You know?Sometimes tears came and one did not know why.

Trujillo: Other times he became very aggressive: he shouted, he hit people, damaged things, he didn't stay still ... The brain area where protein spots begin to appear also has to do with emotions.Therefore, Alzheimer's patients have these symptoms of emotional instability.

Betancur: I tried to be the best possible, but one sometimes also gives impatience.One would like to run because one is for God, what am I going to do?I mean, sometimes, literal, I sat down to cry.

Trujillo: Gladis also had to deal with his dad became addicted to alcohol and drugs.To facilitate things, he decided to take his mother at home.As he had to take care of most of the time, he had to stop working.The economic situation was criticized.In addition to the expenses of the house, Gladis had to pay the transport to make his mother's proceedings, claim medicines, ask for medical exams.And, of course, Magnolia needed special things: food supplements, diapers ...

Betancur: In those my daughters' dad was also given to leave the house.20 years of marriage and they also ended up so much situation.You know that you have to neglect everything because it is that patient there that is the one that requires you all the time of one.

Trujillo: Not all the brothers helped her, and those who did was only at specific times and for a short time.Nor did they give much money and was not constant, so Gladis's eldest daughter, who was one6 years old and was the most helped with the care of Magnolia, decided to start working to contribute economically.

Gladis's social circle was reduced.And not only because I no longer had time to leave, but because people stopped looking for her.His friends moved away, even the extensive family.

Betancur: People daily are excuses: "Oh, it's that I don't go, oh, because I don't like to see her like this".Others: "Oh, no, she, she shouts a lot, then oh, no".But not even one call for one: “How are you?How is the mother? "I mean, no.They moved away at all.

Trujillo: He only mentions a few people who were with her all the time.Among those is its cousin Francisco, the nurse of the neuroscience group.

Some time later, Magnolia had a very strong seizure.This can happen in some patients with advanced Alzheimer's.I couldn't even feed itself.

Gladis increased his responsibilities.Now he had to do absolutely everything for his mother.Moments of impatience, despair, impotence, but despite the deterioration, were not lacking...

Betancur: one is always like hoping that they will be relieved, although it is in the background, but one is always good, suddenly...

Trujillo: Suddenly if I strive, suddenly if I take care of her better, suddenly if I try to speak to her, suddenly if I help her to resist a little more until science finds something ... but those illusions lasted little.

Betancur: one knowing that ... that is there but that it is not.That is, what quality of life has such a person.That if she has a pain, that is, she does not know how to say where it hurts.I mean, it's like, like a baby.

Trujillo: In 20one7, when he was 60 years old, Magnolia became ill of pneumonia.As Gladis tells, he did not complain about any pain.They only knew that it was serious about the high fever and the results of the exams they made.He was already very deteriorated, so his doctor preferred to give him all the necessary medications and care at home.But not aguantó mucho tiempo.He died in the days, after having lived more than a decade with Alzheimer's diagnosed.

Gladis is 42 years old and so far has no symptoms of the disease.It is still closely linked to the neuroscience group of Antioquia.Since 20one3, he is voluntary in a clinical trial that includes 252 people who could have the mutation.Among those is also Francisco's mother, the nurse.And, as usually happens in these studies in humans, a part of the people have been applying a placebo.To the other part, an experimental molecule that, to function, may help treat the disease.They hope that the final results of the study will leave in 2022.

Finally, how do you feel to live as with that fear that ... that there is something there?

Betancur: Well...How do I tell you, one tries, one tries ... not to give importance, but still, there is always a fear.And more than all my daughters: if it doesn't give me, they are saved.If it gives me, one says, there is a probability that they also continue.

Trujillo: And as there was Tatiana, her eldest daughter, I asked her the same question ...

Tatiana Rojo: Well, let's say that at that time I fear I don't feel.Well, for something the study of neurosciences has lasted so long and I say if that was not working long ago they would have finished it.

Trujillo: In fact, since 20one5 they are studying a case that could be the most important in these 30 years of research.At that time they discovered a woman in her database called Aliria Piedrahita.Although he was 72 and the paisa mutation, he had not developed disease symptoms.

When they did detailed studies in a hospital in Boston, they discovered that he had another mutation that prevented there being a lot of tau, the garbage that forms the black crowns around the stains or senile plates.That made him not have symptoms of the disease.In a nutshell, in Aliria's biology could be the answer to find the cure of Alzheimer's, and not only that of this hereditary and early type.

In 20one9, Dr. Francisco Lopera and his colleagues published the case of Aliria in Nature magazine.A year later, Aliria died of cancer when she was about to turn 78 and the symptoms had just begun.But there did not end its contribution to this investigation: the family donated the brain so that they could continue studying it and understand the way it worked.If they manage to imitate what that brain did in a person with Alzheimer's, they could delay symptoms or make them less strong.

Francisco, who is currently 70 years old, does not dare to say how long the results of Aliria's brain would leave.Insists that he will continue to be involved in the investigation until he can.And even when he is not, other people will continue it.If one day they manage to find the cure of Alzheimer.

Alarcón: The neuroscience group of Antioquia continues to look for other people who have the same peculiarity of Aliria, not only in that region.Other neurodegenerative diseases also investigate.

If you live in Colombia and you have a relative with Alzheimer's.If you want more information, we have put a link in the episode description.

David Trujillo is a carriente producer.He lives in Bogota.Thanks a nuestra productora Lisette Arévalo por entrevistar al doctor Kenneth Kosik y darle fuerza a este episodio.

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 of Ambulant Studies, it occurs and mixes in the Hindenburg Pro program.

Radio Ambulante tells Latin America's stories.I am Daniel Alarcón.Thanks por escuchar.

Eliezer Budasoff: Hi, I'm Eliezer Budasoff, presenter of El Wil.20 years ago, when the recession had Argentina to the neck, the government restricted the amount of money that each person could get out of the banks.That was called El Corralito...and caused a social outbreak that marked generations.

Crowd: Let them leave, let them go ...!

Manifestant one: Everyone has to go!

Manifestant 2: They have touched everyone's pocket, people are hungry!

Budasoff: this week, in the thread: the anniversary of the corralito and its repercussions in a country that today suffers a deep crisis again.Listen to it on Friday at Spotify or your favorite podcast application.

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