For decades, the small Colombian town of Yarumal has been shrouded in both tragedy and scientific intrigue.
Nestled in the mountains of northwestern Colombia, this unassuming village of around 41,500 people has been dubbed ‘the village cursed with Alzheimer’s’—but now, it may also be the place that unlocks a cure for one of the world’s most devastating diseases.
Yarumal’s notoriety stems from an unusually high rate of early-onset Alzheimer’s disease among its residents.
Unlike the typical form of Alzheimer’s, which usually strikes people in their late 60s or 70s, many in Yarumal begin showing symptoms as early as their 30s or 40s. Tragically, many die in their 50s, robbed of decades of life and memories.
The culprit? A genetic mutation known as E280A, or the ‘paisa mutation’, which can be traced back to a single common ancestor.
This mutation, passed down through generations, affects an estimated 6,000 people in the region. If you inherit it, the odds are heartbreakingly high that you’ll develop Alzheimer’s—and at a much younger age than most.
But amid this generational heartbreak, scientists have found a glimmer of hope. For over 40 years, researchers including Dr Kenneth Kosik from the University of California Santa Barbara and Dr Francisco Lopera from Colombia have studied Yarumal’s families, searching for answers.
Their work was chronicled in Jennie Erin Smith’s book, Valley of Forgetting: Alzheimer’s Families and the Search for a Cure.
Their breakthrough came with the discovery of Aliria Rosa Piedrahita de Villegas, a woman who carried the deadly paisa mutation but defied the odds. While her siblings and children succumbed to dementia, Aliria lived to 77 with her memory and cognitive abilities intact, eventually passing away from cancer rather than Alzheimer’s.
How did Aliria escape the fate that befell so many of her relatives? The answer, it turns out, lies in her DNA. Not only did she carry the E280A mutation, but she also had two copies of another extremely rare genetic variant known as the Christchurch mutation (a variant of the APOE gene).
This rare combination appears to have protected her brain from the ravages of Alzheimer’s. When scientists examined her brain after her death, they found something remarkable: although she had the same build-up of amyloid plaques (the sticky protein clumps associated with Alzheimer’s) as her affected relatives, she had almost none of the tau tangles that typically cause the most damage in the disease.
In other words, her brain had the ‘bad’ plaques, but not the ‘bad’ tangles—and that made all the difference.
Alzheimer’s disease is the most common form of dementia, affecting more than 400,000 Australians and around 44 million people worldwide. It’s a progressive, incurable condition that slowly erases memory, thinking skills, and independence. The World Health Organisation predicts that by 2050, 115 million people globally will be living with Alzheimer’s.
While we know that age, genetics, and lifestyle factors (like diet, exercise, and social engagement) all play a role, the exact causes of Alzheimer’s remain elusive. Treatments can help manage symptoms, but there is currently no cure.
That’s why the discovery in Yarumal is so exciting. If scientists can understand how the Christchurch mutation protected Aliria’s brain—essentially blocking the formation of tau tangles despite the presence of amyloid plaques—they may be able to develop new drugs or therapies that mimic this effect for everyone.
To understand why this discovery is so important, it’s helpful to first grasp how Alzheimer’s disease typically damages the brain.
One of the main culprits is the build-up of amyloid plaques—sticky clumps of protein that accumulate between nerve cells, interfering with their ability to communicate.
Another is the formation of tau tangles—twisted strands of a different protein that develop inside brain cells, ultimately leading to cell death.
Most people with Alzheimer’s have both plaques and tangles, which together cause widespread cognitive decline. However, in the case of Aliria, her brain was found to have only the amyloid plaques and not the tau tangles.
Remarkably, this absence of tangles allowed her to remain mentally sharp for decades, despite having the gene mutation that normally leads to early-onset Alzheimer’s.
Scientists are now racing to unravel the secrets of the Christchurch mutation. If they can figure out how it blocks tau tangles, it could lead to a new generation of treatments that prevent or slow Alzheimer’s, even in people at high genetic risk.
While the Yarumal mutation is rare, the lessons learned could benefit people everywhere—including the 1 in 12 Australians over 65 living with dementia. It’s a reminder of the power of medical research, and the importance of supporting studies that look at both genetics and lifestyle.
What are your thoughts on the connection between genetics and disease prevention? Do you think breakthroughs like this should influence how we approach medical research or healthcare funding?
Have you or someone you know been affected by dementia? Feel free to share your insights or experiences in the comments.
Also read: Could AI be the key to catching dementia early? Here’s what experts say
