The town of Yarumal in Colombia is famous for all the wrong reasons: it has the world’s largest population of people with Alzheimer’s disease.

In Yarumal and the surrounding state of Antioquia, 5000 people carry a gene mutation which causes early-onset Alzheimer’s – half of them will be diagnosed by the age of 45, and the other half will succumb by the time they are 65.

Locals call the disease La Bobera, “the foolishness”, and the village bears uncanny parallels with the fictional Macondo in Gabriel Garcia Marquez’s novel One Hundred Years of Solitude, where people suffer memory disorders and hallucinations. But while Yarumal’s “curse” is well known, no one knew how the mutation first appeared.


Now researchers have traced the ancestry of the mutation, concluding that it was probably introduced by a Spanish conquistador early in the 17th century.

Ken Kosik at the University of California, Santa Barbara, and colleagues collected blood samples from 102 people in Antioquia and sequenced their genomes. The mutation causing this form of early-onset Alzheimer’s is called E280A and is found in a gene on chromosome 14. The team, which includes Francisco Lopera of the University of Antioquia, who has been working with the families for decades in Colombia, found that 74 people had the mutation.

Because Kosik’s team had information on the genome sequence around the mutation, they could use something called identity-by-descent analysis to determine how the people in the study were related. The analysis suggested the mutation arose from a common ancestor around 375 years ago.

Genetic profile

The geneticists then compared the genetic profile of an Antioquian carrier of E280A against genetic profiles from three potential continents of origin, and the evidence pointed to Western Europe.

This is consistent with a Spanish origin for the 17th-century carrier of the initial mutation, the team say. The conquistadors – soldiers and explorers of the Spanish Empire – began colonising Colombia in the early 16th century, and Yarumal itself was founded in 1787.

“It’s hard to explain why all these people would share such a large chunk of DNA if there hadn’t been a common founder,” says Kosik.

“Putting the genetic data and the historical records together, the assumption that the mutation was introduced by one Spanish conquistador is very likely,” says Rita Guerreiro, a geneticist at University College London. “I think it is fair to conclude from this study that the history of Yarumal and the history of E280A are one and the same.”

One reason that 99 per cent of Alzheimer’s drug trials fail is because the drugs are tested after the disease has taken hold. Yarumal is one of few places in the world where researchers can be sure that a sizable proportion of people will develop Alzheimer’s. This provides an ethical reason to test new drugs on people before they show symptoms.

One of the problems with diagnosing Alzheimer’s at an early stage is that it currently requires a hospital and a lengthy, expensive procedure to look for signs of amyloid plaques in the brain.

“What is needed is a simple memory test that can be carried out by a nurse on a home visit,” says Mario Parra, of Herriot Watt University in Edinburgh, UK. Parra and colleagues are developing just such a test and have trialled it in Antioquia.

To know or not

The people recruited for genome sequencing in Antioquia were not told whether they carry the E280A mutation. “We made a decision, with a great deal of agony, that we wouldn’t tell them as there are no genetic counsellors over there,” says Kosik.

To illustrate the importance of counselling, Kosik recalled a conversation he’d had with a young man. “There was a 24-year-old kid who said he’d want to know the outcome of his test. ‘But there’s no treatment,’ we said. The boy put his hand in the shape of a gun to his head.”

The young man was indicating that he would kill himself, even though if he does have the mutation his symptoms will not appear for two decades. Another person, a young woman of 28, came to the researchers saying she wanted to have children but was afraid of passing on the gene.

Kosik says sometimes he thinks the decision not to tell participants their genetic status was a good one, but that perceptions about genetic testing are changing and that the idea of not telling participants will be difficult to sustain.

James Pickett, head of research at the Alzheimer’s Society, UK, was encouraged by Kosik’s discovery. “There’s been a lack of clinical trials looking at inherited Alzheimer’s disease, so new research that helps us to understand the origins of a genetic mutation across generations is interesting,” he says.

Journal reference: Alzheimer’s and Dementia, DOI: 10.1016/j.jalz.2013.09.005

If you’re concerned about Alzheimer’s, you can read more in our article about the five most likely ways to beat dementia.

Image credits (top to bottom): Raul Arboleda/AFP/Getty Images