Scientists in London have identified a type of genetic mutation that appears to protect against late-onset Alzheimer’s disease.
For their paper, published in the Annals of Human Genetics, the researchers studied DNA samples taken from more than 10,000 people. They identified a class of gene mutations—or variants—that they said appear to protect a pathway critical for cell survival.
Calling his team’s results “quite encouraging,” study author David Curtis from the University College of London Genetics Institute said that the genetic variations his team identified “make Alzheimer’s disease less likely to develop.”
“Drugs which have the same effect might also be protective,” Curtis said in a news release.
The research built on previous studies in mice and rats, which suggested that inhibiting the mutations could protect against Alzheimer’s disease. The new paper marks the first time, the scientists said, that the same effect has been demonstrated in genetic samples from people.
Of the DNA samples that were analyzed, half came from individuals with Alzheimer’s. The other 5,000 samples came from people without any dementia.
In total, the researchers examined all DNA sequence mutations in more than 15,000 genes, including more than one million individual variants, to identify genes in which damaging mutations were more common in people with or without Alzheimer’s disease.
“Here’s a natural experiment in people that helps us understand how Alzheimer’s disease develops,” Curtis added. “We can see that the impact of having particular variants is a reduced likelihood of developing Alzheimer’s disease.”
The gene mutations reduced the functioning of proteins called tyrosine phosphatases, which are known to impair the activity of a cell signaling pathway known as PI3K/Akt/GSK-3β. This pathway is important for cell survival.
Researchers believe the PI3K/Akt/GSK-3β signaling pathway could be a key target for therapeutic drugs and the findings also strengthen evidence that other genes could be linked to either elevated or reduced risk of Alzheimer’s disease.
“Finding DNA variants that modify the risk of Alzheimer’s disease is useful as it may help us develop drugs which target the same proteins,” Curtis said. “As our understanding improves, there may be opportunities to intervene with treatments to prevent the disease from progressing.”
Late last year, researchers drew international coverage when they announced they had identified a rare gene mutation that seemingly prevented a woman from developing Alzheimer’s for decades.
Scientists said the research, published in the journal Nature Medicine, presented a tantalizing clue for why some people are resistant to developing Alzheimer’s.
Like many members of her extended family, the woman, from Medellín, Colombia, carried a gene mutation called presenilin 1. This gene is known to cause early onset Alzheimer’s. In fact, researchers said family members with the genetic mutation have a 99.9 percent risk of developing Alzheimer’s as early as their 30s.
However, the woman did not develop Alzheimer’s until her late 70s. Scientists suspect the disease was held at bay by another extremely rare gene mutation the woman had called APOE3 Christchurch—or APOE3ch—named after Christchurch, New Zealand, where it was first identified.
At virtually the same time, another set of researchers identified genetic mutations related to autism that may play a role in the neurodegenerative disease as well.
The study, out of Tel Aviv University, pinpointed thousands of genetic mutations in aging human brains that overlapped with mutations involved in autism and intellectual disability. They also found that many of these mutations occurred in the cell skeleton/transport system, a network of proteins that help organize cells.
