Scientists find gene variants that could lower Alzheimer's risk

Scientists have identified a class of genetic variants that appear to offer protection against Alzheimer's disease, the most common cause of dementia.

A team from University College London (UCL) conducted a DNA study of more than 10,000 people and found that certain naturally occurring gene variants reduce the functioning of proteins that impair the activity of a cell signalling pathway important for cell survival.

Published in Annals of Human Genetics, this research marks the first time such an effect has been demonstrated in human beings.

Encouraging results

The latest research builds on previous work which suggested that specific genetic variants could protect against Alzheimer's by inhibiting tyrosine phosphatases, which affect the cell signalling pathway known as PI3K/Akt/GSK-3B. Researchers believe this pathway could be a good target for therapeutic drugs.

UCL's study was based on analysis of DNA from 10,000 people, half of whom had Alzheimer's. Researchers examined DNA sequences in over 15,000 genes and discovered that risk of the disease is lower in people with variants in a particular class of genes, which code for tyrosine phosphatases.

One of the key takeaways is that drugs which have the same effect as these genetic variations could also lower the risk of Alzheimer's. There are already some drugs that act on tyrosine phosphatases, but they have yet to undergo clinical testing.

The study's lead author, Professor David Curtis of the UCL Genetics Institute, said these results are "quite encouraging". He noted the findings can be viewed in terms of a "natural experiment" that improves understanding of how Alzheimer's disease develops.

"As some people have these genetic variants and some don't, we can see that the impact of having particular variants is a reduced likelihood of developing Alzheimer's disease," he added.

Professor Curtis also said the results tell a "consistent story" of activity in the PI3K/Akt/GSK-3B signalling pathway having a protective effect, which is in line with findings from previous research.

Stronger understanding

Other outcomes of the UCL research included evidence implicating a gene called C1R, which was not previously known to affect Alzheimer's risk, but has been connected to periodontal Ehlers-Danlos syndrome, a disease involving chronic gum inflammation. These conclusions link to earlier studies which indicated that gum infections may increase the risk of Alzheimer's.

In 2019, UCL was involved in a project that identified five new risk genes for the disease.

Professor Curtis said the work being done by researchers all over the world is helping to improve early detection of Alzheimer's, which can make treatment much more effective.

"As our understanding improves, there may be opportunities to intervene with treatments to prevent the disease from progressing," he added.

There is currently no cure for Alzheimer's, but there are various drugs and treatments that can ease its symptoms or slow the progression of the disease.

The medical community also recommends getting lots of exercise, eating well and maintaining a generally healthy lifestyle to reduce the risk of Alzheimer's.