February 26, 2024


Researchers have taken a major step toward a blood test that can predict the risk of dementia more than a decade before patients are formally diagnosed with the condition.

Hopes for the test were raised after scientists discovered biological markers for the condition in blood samples collected from more than 50,000 healthy volunteers enrolled in the UK Biobank project.

Analysis of the blood identified patterns of four proteins that predicted the onset of dementia in general, and Alzheimer’s disease and vascular dementia specifically, in older age.

When combined with more conventional risk factors such as age, gender, education and genetic susceptibility, the protein profiles enabled researchers to predict dementia with an estimated 90% accuracy almost 15 years before people received clinical confirmation of the disease.

More than 55 million people worldwide live with dementia, a figure expected to reach 78 million by 2030. Around 70% of all dementia is caused by Alzheimer’s disease, with vascular dementia, caused by blood vessel damage, accounting for 20% of make up the cases. .

“We hope to develop this as a screening kit that can be used in the NHS,” said Prof Jianfeng Feng, who holds posts at the University of Warwick and Fudan University in China.

A flurry of recent studies have shown the potential for blood tests to flag patients likely to develop dementia. Armed with such information, doctors can determine which patients to expedite for further assessments, including full diagnostic testing for Alzheimer’s.

Confirming the disease early is crucial if patients are to benefit from two new Alzheimer’s drugs, lecanemab and donanemab, which are being reviewed by the UK medicines regulator. If licensed, the National Institute for Health and Care Excellence will look at the costs and benefits before deciding whether to make it available on the NHS.

The US drug regulator, the Food and Drug Administration, has approved lecanemab and is expected to rule on donanemab soon. European regulators are still reviewing both drugs.

Since lecanemab, a synthetic antibody therapy created by Biogen in the US and Eisai in Japan, made headlines in 2022 for slowing Alzheimer’s disease, doctors and medical charities have warned that the health service is not ready to deliver such drugs.

For patients to receive lecanemab or donanemab, they will need to have early-stage Alzheimer’s and have a lumbar puncture or a PET scan to confirm the presence of amyloid protein in the brain. Toxic clumps of amyloid are one of the hallmarks of Alzheimer’s disease. But Alzheimer’s Research UK estimates that only 2% of eligible patients receive such tests.

Work is ongoing to develop and implement simple blood tests to diagnose Alzheimer’s, but even with rapid diagnosis, challenges remain. The new drugs must be injected into patients every two weeks, and because of the potentially fatal side effects, patients need regular MRI scans to check for brain swelling or bleeding.

For the latest study, blood samples from 52,645 British adults without dementia were collected and frozen between 2006 and 2010 and analyzed 10 to 15 years later. More than 1,400 participants went on to develop dementia.

Using artificial intelligence, the researchers looked for connections between nearly 1,500 blood proteins and the development of dementia years later. Write in Natural agingthey describe how four proteins, Gfap, Nefl, Gdf15 and Ltbp2, were present in unusual levels among those who developed dementia of all causes, Alzheimer’s disease or vascular dementia.

Higher levels of the proteins were warning signs of disease. Inflammation in the brain can cause cells called astrocytes to overproduce Gfap, a known biomarker for Alzheimer’s. People with elevated Gfap were more than twice as likely to develop dementia as those with lower levels.

Another blood protein, Nefl, is linked to nerve fiber damage, while higher than normal Gdf15 can occur after damage to the brain’s blood vessels. Rising levels of Gfap and Ltbp2 were highly specific to dementia rather than other brain diseases, the scientists found, with changes occurring at least 10 years before people received a dementia diagnosis.

The researchers are talking to companies to develop the test, but said the cost, currently at several hundred pounds, would need to come down to make it viable.

Dr Sheona Scales, the director of research at Alzheimer’s Research UK, said: “This new study adds to the growing body of evidence that looking at levels of certain proteins in the blood of healthy people can accurately predict dementia before symptoms develop.”

Further studies are needed to understand how well such tests work in more diverse populations. Scales added: “Even when tests show promise in studies like this, they still need to go through regulatory approval before they can be used in a healthcare setting.

“Blood tests show great promise, but so far none have been validated for use in the UK. Working with Alzheimer’s Society, NIHR, and with generous funding from People’s Postcode Lottery players, we are funding research to provide the evidence the NHS needs to move forward with blood tests to diagnose Alzheimer’s.



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