But she was just one patient. This raises an unfortunate question: Could this case hold the key to a new way to prevent Alzheimer’s disease? Or was she once?
In the year In a study published Wednesday New England Journal of MedicineResearchers report that 27 members of the same Columbia family carry the genetic risk of Alzheimer’s disease with a single Christchurch copy. Cognitive decline in this single group was delayed by nearly five years—suggesting that a gene-mimicking drug may have the same effect.
“We’re taught in medicine to be careful not to jump to too many conclusions,” said Joseph F. Arboleda-Velasquez, MD, an associate scientist at Mass Eye and Ear in Boston. of the study. “Maybe it has to do with what she ate or didn’t eat. Maybe it’s something to do with the water in the house. The idea of finding 27 people – some living in urban areas, some living in rural areas – increases our confidence in the findings – showing that the results are replicable.
Key insight from low maintenance rates
Francisco Lopera, a neurologist at the University of Antocia in Medellin, Colombia, began caring for patients with hereditary Alzheimer’s disease four decades ago.
Cognitive impairment begins when people are in their mid-40s. Full-blown dementia appears before age 50. Patients died in their 60s. Researchers have traced the disease to a mutation in a gene called presenilin 1, which is now known to be passed on to about 1,200 people in a family.
Piedrahita de Villegas showed scientists that it is possible to resist this terrible genetic fate. But for that to translate into broader medical understanding for a particular patient, scientists need proof that a gene can have a beneficial effect — and that it can do the same in other people.
Humans carry two copies of the APOE gene inherited from each parent. According to Yaquil T. Queiroz, a clinical neuropsychologist at Massachusetts General Hospital, having two copies of the Christchurch edition, as Piedrahita de Villegas did, “is very rare.” So they started looking for people who only had one.
A person carrying an Alzheimer’s risk mutation and the Christchurch copy gave the first clue. At the age of 51, a brain scan revealed that he had mild cognitive impairment Elevated beta-amyloid protein plaques, a hallmark of Alzheimer’s. But surprisingly, he had limited exposure to a specific Alzheimer’s-related protein called tau, and at age 54, he developed mild dementia years later than expected.
“This was a sign that having a copy could be protective,” Queiroz said. The team found 26 people with this genetic makeup. Not all patients experienced cognitive impairment, but among those who did, symptoms were delayed, starting five years after Christchurch did not. Dementia was also delayed by four years.
The discovery that a single copy of Christchurch provides a degree of protection is a promising sign for scientists trying to develop treatments. If two copies are necessary, the bar for a new drug can be very high – it must be extremely effective to get any benefit. But it is a good sign that a low level of the gene prevents the occurrence of disease. It suggests that partial mimicking of the function of the Christchurch gene may work.
“I think this is a very important study, and the results are very important,” said Yadong Huang, director of the Center for Translational Development at the Gladstone Institute, an independent biomedical research organization based in San Francisco. Huang He did not participate in the study, but his laboratory showed it last year Christchurch Mutation It has benefits in Alzheimer’s disease-prone mice and in human brain cells in plates. Still, he says, until now there has been a critical gap in knowledge about how it affects people in the real world.
Rare patients lead to new treatments
For years, Alzheimer’s research has focused on clearing sticky amyloid plaques that accumulate in the brain. A few treatments have shown success, but they are far from a cure. The new research shows promise for a different biological target: drugs that mimic the rare Christchurch variant of the APOE gene.
John Hardy, a neurogenetics expert at the UK Dementia Research Institute at University College London, said pharmaceutical companies have traditionally been less enthusiastic about APOE as a difficult target, but that is changing.
“Interest is growing, and this discovery is part of the reason,” Hardy wrote in an email.
As the next step, researchers have prepared a Experimental antibody drug It looks like Christchurch. When they gave mice genetically engineered to develop Alzheimer’s symptoms, the drug reduced the accumulation of tau tangles — a sign they were on the right track, they found.