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Genes linked to Alzheimer’s may help calculate your risk of getting it

Findings from the biggest genetic study of Alzheimer’s to date could help people at high risk of the disease take action to delay or prevent symptoms

Health 4 April 2022

2CE12PN Amyloid plaques forming between neurons. Beta-amyloid protein disrupting nerve cells function in a brain with Alzheimer's disease

Illustration of amyloid plaques in the brain of a person with Alzheimer’s disease

nobeastsofierce Science/Alamy

The biggest Alzheimer’s study of its kind has more than doubled the number of genetic variations known to be implicated in the disease. The research points to a future where people could be given a genetic risk score for their potential to develop the condition and personalised strategies for prevention and treatment.

Alzheimer’s is the most common cause of dementia, affecting more than 850,000 people in the UK. About 60 to 80 per cent of the risk for the disease is thought to be genetic.

To find more of the genetic factors responsible, Rebecca Sims at Cardiff University in the UK and her colleagues looked at the the genomes of more than 100,000 people who had Alzheimer’s or had a parent with the condition, and compared them with over 600,000 people with no family history of the disease.

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This is much more than the number of people with Alzheimer’s analysed by any previous genome-wide association study (GWAS). “The last major GWAS in Alzheimer’s had about 22,000 people with Alzheimer’s in its initial set-up,” says Sims.

The analysis confirmed the role of 33 gene variations that had previously been linked to the disease and added a further 42 specific gene variations to that list.

Sims says no variation seems more significant than any other. “Part of what this study shows is how complex this disease actually is and how multifactorial it is,” she says.

But it does highlight the role that microglia, immune cells in the brain, can play in the disease, says Sims. “Years ago, we were only looking at neurons and how they might be involved in Alzheimer’s, but now we know that these cells are really important too.”

This research will make it easier to ensure people are given the best treatment for them, she says. For example, Alzheimer’s in one person may be caused by variations involving microglia, whereas in another it could be due to dysfunctions in fat metabolism.

“A lot of drugs may be more useful in certain people than others depending on what type of pathways are involved,” says Sims. “Potentially, the drugs will have a bigger effect if we target the right pathways.”

The team found that including these newly discovered gene variations improved the accuracy of genetic risk scores, which could be used to inform people about their potential to develop the disease. “If someone’s got a really high risk of developing Alzheimer’s, potentially they can start taking drugs earlier in life to help either delay it or even prevent it,” says Sims.

One limitation of the study is the fact that nearly all the participants in it were white – in common with many other GWAS. This is by design, as different populations of people will have different genetic variations and so it is harder to make comparisons between people with and without a specific disease in a more diverse study group.

Sims says it is unclear to what extent the findings will be applicable to people of colour. “We need this research funded for other populations.”

“I am incredibly excited by the implications of this study,” says Catherine Kaczorowski at the Jackson Laboratory in Bar Harbor, Maine. The finding that genetic risk scores for Alzheimer’s can be made more accurate by including these new genetic variations is particularly significant, she says.

“This study is important because it provides the opportunity to identify novel biological pathways underlying Alzheimer’s disease risk,” says Jennifer Yokoyama at the University of California, San Francisco. Genetic risk scores could be useful for analysing the effectiveness of interventions aiming to prevent Alzheimer’s, she says.

Journal reference: Nature Genetics, DOI: 10.1038/s41588-022-01024-z

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