Among the largest family in the world suffering from Alzheimer's disease, an elderly woman may hold the key to future prevention.
For generations, thousands of her relatives in the city of Medellin, Colombia, have been affected by a genetic mutation (known as E280A), leading to the early onset of dementia – what the locals call "La Bobera" or " nonsense. "
This particular genetic trick affects only a small subset of Alzheimer's patients, many of whom live in this city, and almost always leads to a cognitive decline beginning at the age of 44.
For decades, neurologists have been fascinated by this mutation and the family that carries it. But of the 6,000 or more living members in this large extended clan, there is one individual who stands out.
Although it has the same genetic risk as many of its relatives and a brain full of Alzheimer's traits, the memory of this woman has remained remarkably stable.
In fact, neurologists claim that this lady did not show any signs of cognitive decline until she was 70, which is three decades later than expected.
Now, researchers believe they have figured out why and
Scanning the brain and sequencing the genomes of 1
The authors suspect two copies of a gene called APOE3 Christchurch are responsible for her happiness, as the woman appeared to be the only one in the group to have both. Those who have only one copy of the variation still show early-onset cognitive decline.
Neurologist Yadong Huang of the Gladstone Institutes in San Francisco, who was not involved in the research, told Science that the case was "very special" and could open new avenues for research and therapy.
But while Michael Grecian of Stanford University agrees, calling the study "an excellent and thought provoking" study, he reminded STAT News that this is just one case and an extremely rare one.
In fact, this woman's "genetic lineage," he says, may be completely unique, and this could complicate his effect on other patients.
The authors of the study, on the other hand, believe that its special genes are an advantage.
"She has a secret in her biology," said Colombian neurologist Francisco Loper to The New York Times .
"This case is a great window for discovering new approaches."
When scanning a woman's brain, researchers say they have found the highest levels of amyloid protein.
These lumps are hallmarks of Alzheimer's disease, and while they were once thought to cause the disease, there are no drugs that have directed them to work yet. Instead, another trait known as tau began to receive more and more attention.
Just like her relatives, the genetic mutation of a Colombian woman, E280A, is associated with the overproduction of amyloid plaques. But instead of moving on, the authors believe that its additional mutations somehow delay the process, potentially impeding the rapid spread of tau.
At this point, the idea is simply a hug, but previous studies have linked variations in APOE, a major cholesterol-carrying protein, to Alzheimer's disease and tau.
"This study highlights the importance of APOE in the development, treatment and prevention of Alzheimer's disease, not to mention the profound impact that even a research volunteer can have in combating this terrible disease," said the Institute's neurologist Eric Reiman
"We hope that our findings will increase and inform the discovery of APOE-related drugs and gene therapies so that we can apply them to the test in treatment and prevention studies in as soon as possible. "
However, this may simply be desirable. Thousands of other genomes play, and although APOE is a good lead, many more studies will need to be done before we can say for sure what its relationship to this common neurological disease is.
The study was published in Natural Medicine .