Genetic trait that virtually ‘guarantees’ Alzheimer’s identified (2024)

Researchers have identified a genetic trait that makes it virtually “guaranteed” a person will get Alzheimer’s, in a discovery that may pave the way to better targeted treatments and earlier diagnoses.

A study found that having two copies of a specific gene makes it almost inevitable that a person will eventually develop symptoms.

Experts said the discovery may help the development of targeted treatments and could enable genetic testing and earlier interventions.

More than 900,000 people have dementia in the UK, the majority of whom have Alzheimer’s. There is no cure for the disease, although treatments have been found to slow its progress.

In the study, researchers in Barcelona found that 95 per cent of people over 65 with two copies of the APOE4 gene variant developed signs of the disease. About one in four people in the UK have one copy of this gene, while one in fifty — equivalent to more than a million people — have two.

“This gene has been known for over 30 years and it was known to be associated with a higher risk of developing Alzheimer’s disease,” said Dr Juan Fortea, director of the memory unit of the neurology service at Sant Pau Research Institute, and lead author of the study.

“But now we know that virtually all individuals with this duplicated gene develop Alzheimer’s biology.”

The researchers said their findings effectively amounted to the discovery of a new genetic form of the disease, because the presence of both genes was such a useful predictor for the condition.

The findings, published in the journal Nature Medicine, are based on data from more than 10,000 people and more than 3,000 brain donors.

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Siân Gregory, the research manager at Alzheimer’s Society, said: “I think it’s definitely a breakthrough for the field in terms of how we think about the causes of Alzheimer’s disease.” She said it would make it easier to predict when symptoms might start and enable doctors to give people more advice at diagnosis.

Dr Richard Oakley, Alzheimer’s Society’s associate director of research and innovation, said: “Understanding the causes of the disease in greater detail is vital and can unlock new ways of diagnosing, treating and caring for people affected by Alzheimer’s disease in the future.

“The insights from the study suggest that in the future it could be important to take into account a person’s genetics when planning how to reduce their risk of developing Alzheimer’s disease, or when considering their treatment if they already have the disease.”

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Previous studies have shown that having at least one APOE4 gene variant almost triples the risk of getting the disease, while having two copies increases the risk by up to twelvefold.

In the latest research, a majority of people with two copies of APOE4 showed some signs of the disease by the age of 55. By age 65, 95 per cent of them had abnormal levels of a protein known as amyloid in the fluid that surrounds the brain and spinal cord, which is a key sign of Alzheimer’s disease.

Professor Tara Spires-Jones, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute at the University of Edinburgh, said: “This study adds compelling data to suggest that people with two copies of this gene are almost guaranteed to develop Alzheimer’s if they live long enough and that they will develop Alzheimer’s earlier than people without this gene.”

Dr Víctor Montal, a researcher who studies the molecular structure of the APOE gene at the Barcelona Supercomputing Centre, added that the findings could be used to monitor people with this gene from an early age for preventive interventions. Drugs such as donanemab and lecanemab have been shown to slow the progression of the condition in clinical trials.

How advanced are we in the fight against Alzheimer’s?

Despite years of research, Alzheimer’s disease remains a cruel condition that affects hundreds of thousands of Britons each year (Poppy Koronka writes).

It is thought to be caused by a build-up of toxic proteins in the brain that impair memory and reasoning, and close to a million people in the UK have it.

Several recent breakthroughs have shown promise for one day treating the condition, or at least slowing its progression. Last year the drug donanemab was shown to slow cognitive decline by more than a third, leading some to declare that it marked the “beginning of the end” of the disease.

The treatment, which attacks the toxic proteins, can offer some people at least a year of extra time without Alzheimer’s progressing.

Another drug, lecanemab, works in a similar way to donanemab and was found to slow memory decline by 27 per cent over 18 months in a 2022 trial.

Both are yet to be approved for use in the UK, with the National Institute for Healthcare and Excellence, the health regulator, due to release a decision on lecanemab later this year.

Another research development is in blood tests, which seek to identify the disease early and tackle the poor diagnosis rates in Britain. Early trials have shown promise, but widespread use on the NHS is probably quite far off.

The latest research, which identifies a genetic trait so distinctive that researchers argue it effectively amounts to a new form of Alzheimer’s, suggests that genetic testing may one day become a tool in the armoury for diagnosing and treating the condition.

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