Certain genetic variants may reduce an individual’s likelihood of developing Alzheimer’s disease, British researchers report today.
The work is carried out by Professor David Curtis and colleagues at University College London, UK.
They looked at the DNA of over 10,000 people – half of whom had Alzheimer’s disease – to search for gene variants that appeared to be linked to the disease. Results appear today (5 February) in Annals of Human Genetics.
It seems that the highlighted variants limit the action of proteins called tyrosine phosphatases, which in turn impair a cell signalling pathway necessary for cell survival, called PI3K/Akt/GSK-3beta.
The team suggest that inhibiting these proteins could help protect against Alzheimer’s disease, and they also believe that other genes could be linked to a raised or reduced risk of the condition.
Professor Curtis says: “Here’s a natural experiment in people that helps us understand 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.
“These results are quite encouraging. It looks as though when naturally-occurring genetic variants reduce the activity of tyrosine phosphatases then this makes Alzheimer’s disease less likely to develop, suggesting that drugs which have the same effect might also be protective.”
However, such drugs have not yet been tested in clinical trials.
Professor Curtis adds that finding DNA variants which modify the risk of Alzheimer’s disease may help develop drugs which target the same proteins. “As our understanding improves, there may be opportunities to intervene with treatments to prevent the disease from progressing," he concludes.
Curtis, D. et al. Weighted burden analysis of exome-sequenced late onset Alzheimer’s cases and controls provides further evidence for a role for PSEN1 and suggests involvement of the PI3K/Akt/GSK-3beta and WNT signalling pathways.
Annals of Human Genetics 5 February 2020; doi: 10.1111/ahg.12375
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