Researchers in the US have developed a new scoring system to indicate a person’s risk of Alzheimer’s disease. The technique involves analysing a number of different genes to assess an individual’s likelihood of developing the disease as they age. Their findings are reported (21 March) in PLOS Medicine.
Most cases of dementia do not have a single genetic cause, rather variation across numerous genes combines to influence risk. This new study used large amounts of data to understand how genetic variation contributes to the risk of developing Alzheimer’s, and to predict the likelihood of developing symptoms as a person gets older.
Using genetic information from the International Genomics of Alzheimer’s Project, the researchers analysed the genes of 54,162 people (17,008 with Alzheimer’s and 37,154 healthy older people) and identified 31 genetic variations associated with an increased risk for Alzheimer’s. The team then used another data set, Alzheimer’s Disease Genetics Consortium Phase 1, and combined genetic information with the age of onset of Alzheimer’s for 15,795 people (6,409 with Alzheimer’s and 9,386 healthy older people), from which they calculated a ‘polygenic hazard score’ (PHS).
To test whether this score was able to predict who was at risk of developing Alzheimer’s, the researchers applied the scoring system to the Alzheimer’s Disease Genetics Consortium Phase 2 data set, which contains 17,956 people (6,984 with Alzheimer’s and 10,972 healthy older people). The team assigned people to different groups based on their genetic risk, and found that the age at which the PHS predicted people would develop Alzheimer’s symptoms was strongly associated with the actual age of onset.
The team then combined information about how common each of the 31 genetic variants in the PHS was in the wider population with the incidence of Alzheimer’s recorded across the US population. From this, they were able to estimate a person’s Alzheimer’s risk across their lifetime based on their genetic risk score, as well as the yearly incidence rates for developing Alzheimer’s for different risk scores. They found that individuals with the highest PHS were more likely to develop Alzheimer’s, and that the PHS could predict the age of onset of the disease.
To understand how the PHS may alter Alzheimer’s-related changes in the brain, the researchers used data available from two other studies; National Institute of Aging-funded Alzheimer’s Disease Centers and Alzheimer’s Disease Neuroimaging Initiative. Combining information from these two studies, the team found that having a higher PHS was associated with a greater build-up of Alzheimer’s proteins in the brain as well as with worse memory and thinking skills and reductions in brain volume. The authors conclude that the PHS may serve as a way to identify people at greater risk of developing Alzheimer’s disease, and indicate the age at which they may develop it.
Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:
“With 1 million people estimated to develop dementia by 2025 and Alzheimer’s disease responsible for the majority of cases, a better understanding of who is most at risk is crucial for researchers looking for new ways to prevent the disease. We know that Alzheimer’s disease starts to take hold in the brain many years before people show symptoms, and current clinical trials have struggled to test potential new medicines in the early time window when they could be most effective. Being able to detect who is at an increased risk of developing Alzheimer’s could revolutionise the way we evaluate potential new drugs.
“This study is one of a number of initiatives combining different genetic factors to assess Alzheimer’s risk. While these genetic risk scores hold promise as valuable research tools, they will need to be thoroughly evaluated, tested and refined before they could ever be used to help doctors diagnose or treat the disease. This particular study focused on people of European descent and the risk score now needs to be applied in other populations, as we know that Alzheimer’s risk can vary between different ethnic groups.
“This study does not suggest that having a high polygenic hazard score means you will definitely develop Alzheimer’s, nor does a low score mean you are immune from the disease. Genetics is only part of the story and we know that lifestyle factors also influence our risk of developing Alzheimer’s. The best current evidence points to habits we can all adopt to help lower our risk and indicates that what’s good for your heart is also good for the brain. Eating a healthy balanced diet, keeping physically and mentally active, not smoking, drinking in moderation, keeping blood pressure and cholesterol in check and maintaining a healthy weight are all ways to support healthy brain ageing.”