For many years, a small village in Colombia has been dealing with a disease that leaves its residents struggling with severe memory loss.
In Yarumal, a town with around 41,500 people in northwestern Colombia, locals experience Alzheimer’s disease at a rate significantly higher than in many other parts of the world, largely because of a genetic mutation.
This mutation, known as E280A or the ‘paisa mutation,’ has been inherited from a single ancestor, affecting about 6,000 individuals within the community. It results in Alzheimer’s afflicting nearly everyone who carries it.
The mutation is located on the 14th chromosome and leads to an aggressive form of early-onset Alzheimer’s, contributing to debilitating dementia. Those who inherit it can begin showing symptoms as early as their 30s, while the average onset in the United States is around 49.
However, amidst all the pain, researchers have found hope in the unusual genetic profile of one individual. Jennie Erin Smith, who chronicled the journey of neuroscientists from the University of California, Santa Barbara, and Colombia, highlighted their four-decade-long study of Yarumal residents until they discovered Aliria Rosa Piedrahita de Villegas.
Piedrahita de Villegas, who passed away at 77 from cancer, was both a lifelong resident of Yarumal and a bearer of the paisa mutation. Curiously, she never developed Alzheimer’s, even as many in her family were afflicted.
This led scientists to a baffling revelation: although she carried the mutation associated with dementia, Piedrahita also possessed an additional mutation that protected her from the disease.
Now, researchers are eager to delve deeper into this protective effect identified in her brain, which could ultimately help prevent Alzheimer’s in others.
Dr. Kosik reflected, “She was really interesting because she had this mutation that usually leads to Alzheimer’s, but at 70-something, she was still doing fine.”
Thanks to her cooperation in research and her family’s willingness to donate her brain following her death in 2020, significant strides have been made in exploring potential treatments for a condition impacting around 44 million worldwide.
Alzheimer’s disease, a prevalent form of dementia among older adults, affects about 7 million individuals aged 65 and older in the U.S., with over 100,000 fatalities attributed to it annually. The onset of the illness is linked to the accumulation of amyloid plaques and tau tangles in the brain, which ultimately leads to cell death.
Amyloid proteins can form clumps called plaques, and tau proteins can twist into tangles. These block communication among neurons, causing lasting brain damage and eventually Alzheimer’s.
Although the exact cause of the disease remains uncertain, factors like genetic mutations and lifestyle choices—such as inactivity, poor diet, and social isolation—are believed to play a role.
Currently, there’s no cure, but there are treatments aimed at managing symptoms.
Dr. Kosik has possibly uncovered vital insights regarding how Piedrahita de Villegas avoided the disease while the rest of her family did not.
In collaboration with researchers from Massachusetts General Hospital, they discovered that her brain had an unusually high amount of amyloid protein but very little tau protein, which is crucial in developing Alzheimer’s tangles.
“While Aliria had the same plaque overproduction as her family, she lacked the accompanying tangles, which maintained her motor skills and executive functions,” Dr. Kosik noted.
Moreover, her DNA exhibited two copies of a rare gene mutation known as apolipoprotein, or APOE.
This APOE variant, sometimes called the Christchurch mutation, enabled her body to generate lipoproteins that countered the damaging effects of amyloid protein plaques in the brain.
Lipoproteins, made of protein and fat, transport cholesterol through the bloodstream. The main types are HDL (good cholesterol) and LDL (bad cholesterol).
Now, researchers are hopeful that these findings will lead to preventive treatments for those at risk of Alzheimer’s.
Dr. Kosik remarked, “The chance of one rare mutation is small, but discovering someone with two exceptionally rare mutations—alongside a known Alzheimer’s mutation—raises so many questions.”
“Her case garnered significant attention globally, and we learned invaluable lessons from her. Now that she’s gone, it’s crucial that we thoroughly investigate what we’ve found.”
