In Colombia, are there people who hide Alzheimer’s and its cure in their biology?

Francisco Lopera Restrepo defined his path when he accompanied his father to visit his grandmother with dementia.

“My dad was shocked because my grandmother didn’t recognize him, so I suggested taking her to a specialist,” said Lopera, then a first-year medical student at the University of Antioquia in Medellín, Colombia.

The father responded hopelessly: “Son, several have already seen her. Grandma has no cure.”

“So I chalked it up to medical malpractice and thought when I graduated it wasn’t going to happen. And look, here I am 40 years later.”

Lopera, now a 73-year-old researcher at the University of Antioquia, dedicates his life to searching for answers about Alzheimer’s.

His outstanding resume began when in the 1980s he received a 47-year-old patient with a mysterious form of hereditary early Alzheimer’s.

Years later he discovered the responsible mutation, the “paisa mutation”, in reference to the name given to people from the departments of Antioquia, Caldas, Risaralda and Quindío in Colombia.

It was the beginning of arduous studies and findings that recently earned him the Potamkin Prize, known as the “Nobel of research against Alzheimer’s.”

Lopera is the first Latin American to achieve this award since its establishment in 1988.

Alzheimer’s is still an incurable disease and the most common form of dementia, an ailment suffered by more than 55 million people in the world, according to the World Health Organization.

Lopera, a world-leading neurologist in the study of early hereditary Alzheimer’s, spoke with BBC Mundo about his findings and the progress made in finding a cure for the disease.

How did your investigations start?

In the 80s I received a patient from Belmira (Antioquia) who at the age of 47 had lost his memory and could not work.

It was very rare for someone so young to develop Alzheimer’s, when it is normally a disease of those over 65 years of age.

It turns out that the same thing had happened to his father, several brothers and one of his grandparents. He was hereditary.

We published the discovery in a Colombian journal and described it as familial early-onset Alzheimer’s-type dementia, although we did not know which gene was involved.

In 1995, in collaboration with the University of Washington, we clarified that it was a mutation in the presenilin 1 gene that caused early Alzheimer’s.

From there we identified other families with similar cases in various locations in Antioquia. They all had the same characteristic: a young person with memory loss and a family history.

The main achievement that we are recognized with the award is discovering the largest population group in the world with a genetic form of Alzheimer’s and finding the gene responsible: the “paisa mutation”.*

[*Lopera investigó más de 6.000 miembros de decenas de familias en Antioquia que portan la mutación paisa que causa demencia precoz].

It is a 40-year job of more than 100 people.

How do we explain this mutation to those who have never heard of it?

The genetic code has four letters: A for adenine, G for guanine, T for thymine and C for cytosine.

There are millions of strings with those four letters in a particular order. A change from one letter to another is a mutation.

For example, everyone knows what the word table means, but if you change the i to the e, it says mass, nothing to do with it. That is a mutation, an error in the genetic code.

The paisa mutation is an error in the genetic code that causes early-onset Alzheimer’s.

But they also found genes that delay the disease, right?

Nature does not choose and the disease and the cure live within itself.

In Antioquia we find people who have a gene that causes Alzheimer’s and another that cures it. It is outstanding.*

[En 2023, Lopera y su equipo publicaron el caso de una persona que tenía la mutación paisa, pero que además tenía otra mutación que lo protegió de la demencia hasta los 67 años].

These genes that protect against Alzheimer’s are a very important finding because they may be a route to cure and prevention.

If someone carries it and is protected for 20 or 30 years from the symptoms of the disease, the protective gene could be inoculated into a high-risk patient and delay the onset by two or three decades.

That, in a person with the most common type of Alzheimer’s that appears after the age of 65, is practically curing the disease.

The awards also recognized us for having managed to characterize the preclinical stage of Alzheimer’s. By monitoring these populations we define stages without symptoms or memory problems, but with alterations in the brain.

What is happening in Colombia and in particular Antioquia that has allowed you to draw these conclusions?

Someone brought the paisa mutation from Europe 350-400 years ago, according to several studies, and planted it and watered it throughout Antioquia. It’s what we call the “founder effect” and it has been the explanation for several years.

The curious thing is that in Europe this mutation has not been reported until now.

It happens in a similar way in other countries in the region: with Venezuela having the largest recorded focus of Huntington’s disease in the world and in Cuba the one with the highest juvenile hereditary ataxia.

We have also found several cases of juvenile Parkinson’s in other regions of Antioquia.

However, that founder effect explanation may not be 100% true.

For years we believed that the only Alzheimer’s mutation in Colombia was paisa, but a few years ago we launched a campaign throughout the country asking for blood tests from patients with early dementia.

We received 1,000 samples, we analyzed them and only eight had the paisa mutation. In the remaining ones we found another 12 mutations that cause early Alzheimer’s in other departments of the country.

In other countries, families with hereditary Alzheimer’s have also begun to be found, such as in Jalisco, Mexico, where two families have mutations in presenilin 1 that have nothing to do with paisa. Other cases have also been found in families in Argentina, Chile and Brazil.

Antioquia is the focus of these neurodegenerative diseases because here we look for them and make genealogies. When other countries did the same, they began to find families.

Are early Alzheimer’s very different from Alzheimer’s that manifests itself later in life, which is the most common?

Early Alzheimer’s is more aggressive, although there are differences between the early forms themselves.

Families with early genetic Alzheimer’s in Antioquia are different from those in Jalisco.

The clinical picture is very similar: loss of memory, cognitive functions, autonomy and independence that requires a caregiver. But in Jalisco, in addition, the disease produces paralysis of the lower limbs that we do not see in the paisa mutation.

There is a mutation in Valle del Cauca (another Colombian department) that causes the disease at 28-29 years, even earlier than the paisa, which is usually at 44.

In the end, the main difference is the starting time, although they are very similar in their evolution.

How do these families you study live?

They go through three stages.

The first is a preclinical one where there are no symptoms of memory loss or dementia. He is a completely normal person but the protein waste produced by the disease begins to deposit in his brain. Neurons die.

It is a process that can last about 30 years but where the person does not suffer symptoms. Something happens in his brain, but he doesn’t realize that it is silently destroyed.

When the stage of mild cognitive impairment arrives, you experience many difficulties at work because you begin to forget everything. However, he remains independent and autonomous, although affected by memory loss, which causes a lot of anguish. He lasts between two and five years.

When the stage of dementia arrives, the person cannot live alone, but rather with someone who takes care of them and is attentive. It can be a spouse, a child, who is responsible for care.

It is something very difficult for the caregiver who may suffer anguish and depression because it is difficult to care for and manage that patient with dementia.

There is a small percentage with more economic resources who are cared for by an institution, paying to have them cared for.

The last stage lasts about 15 years.

What are the most important questions that remain to be answered about Alzheimer’s?

How to cure and prevent, and it seems to me that it will be easier to answer the second one.

Much progress has been made in understanding the disease, but we still need to find how to attack it, delay it, cure it, and prevent it.

There are clues: the protective genes discovered could allow the development of gene therapies to delay the onset of symptoms. A molecule that mimics the mechanism of action of the protective gene can also be developed.

It takes time and planning because gene therapy can cause adverse effects.

It may take five to 10 years to refine those two pathways and find the definitive way to delay, prevent or cure the disease.

In my group we focus on the search for protective genes. Each can be an avenue for cure or prevention.

How to face the fear caused by Alzheimer’s?

The first thing is not to see it as a tragedy. It is a serious illness, but it must be de-dramatized, seen more as a new way of life.

If you look at it that way, you can adapt to being happy with the illness.

Alzheimer’s has the advantages that it does not cause pain and that the sufferer is not very aware of what is happening. At first, yes, but when the disease progresses you don’t even know you have it.

The patient, in reality, is not the one who suffers the most, but rather his caregivers. But if the family and the environment surround the patient with a favorable environment to be happy, it is possible to achieve it.

Of course, the best thing is not to have the disease and do what you can to prevent it: physical exercise, avoiding stress, sleeping and eating well.

In what areas could progress be expected in the study of Alzheimer’s?

Molecules that improve the disease have already begun to be discovered. They don’t cure it, but they improve it by 25%-30%.

These molecules would mimic the function of protective genes in the brain.

The disease will continue and will not stop, but we will increasingly have more effective molecules and medications.

First a method was discovered that improved 25%, then it was expanded to 30%. Very soon another one will be released that improves 40%, or a combination of medications that improves the disease by 40%-50%.

This is what follows: partial solutions while the definitive one is found.

Click here to read more stories from BBC News Mundo.

You can also follow us on YouTube, Instagram, TikTok, X, Facebook and our new WhatsApp channel, where you will find breaking news and our best content.

And remember that you can receive notifications in our app. Download the latest version and activate them.