Researchers in the UK and China have used proteomics data from the UK Biobank to identify protein biomarkers in the blood that could give warning of dementia years before diagnosis and make it easier to select patients for drug treatment.
The team from the University of Warwick and Shanghai’s Fudan University believe that it is the largest cohort study of blood proteomics and dementia to date, drawing on blood samples from 52,645 healthy participants in the UK Biobank taken between 2006 and 2010.
The frozen samples were thawed and analysed 10 to 15 years later, looking at the presence of 1,463 proteins. Using artificial intelligence, comparisons were made between patients who went on to develop dementia and those who did not, to identify any that could serve as an early warning system.
They found a panel of 11 that – when combined with other risk factors such as age, sex, education level and genetics – was more than 90% effective at predicting dementia, according to a paper published in the journal Nature Aging.
The proteins were able to predict all-cause dementia as well as particular types including Alzheimer’s disease and vascular dementia, and could also open avenues for new research into novel treatments, according to the researchers.
Lead author Prof Jianfeng Feng of Warwick’s computer science department said that testing for the biomarkers could be “seamlessly integrated into the NHS and used as a screening tool by GPs,” identifying people for example who could benefit from early treatment with new disease-modifying therapies for Alzheimer’s disease like Eisai and Biogen’s amyloid-targeting Leqembi (lecanemab).
Some of the proteins, for example glial fibrillary acidic protein or GFAP, have been identified as potential biomarkers for dementia in the past. The size of the study however reinforces GFAP’s role as “an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis, with implications for screening people at high risk for dementia and for early intervention,” write the authors in the paper.
The strongest association was found to be with GFAP and another protein called LTBP2, while a third (NEFL) also has the potential to be used to predict dementia a decade or more before diagnosis.
The finding comes shortly after another large-scale study found that testing of blood for a protein called phosphorylated tau could provide a means of large-scale screening for Alzheimer’s disease.
One commentator – Prof David Curtis of University College London’s Genetics Institute – said the reported associations “are not really strong enough to say that these would form a useful test for predicting who will get dementia in the future,” although he said they could help researchers understand the biological systems involved in the development of dementia.
He also suggested the data for phosphorylated in Alzheimer’s is stronger and will be helpful when effective treatments for the disease become available. Leqembi isn’t approved yet in Europe but has been cleared in the US, China, and Japan.
“We have seen some fantastic progress in the development of blood tests for Alzheimer’s over the last few months,” commented Dr Sheona Scales, director of research at Alzheimer’s Research UK.
“This new study adds to the growing body of evidence that measuring levels of certain proteins in the blood of healthy people could accurately predict dementia before symptoms develop,” she added, while cautioning that more studies in more diverse populations will be needed to verify the tests and predictive models.
Only two out of three people with dementia in the UK ever receive a formal diagnosis, and the current gold standard diagnostic tests – lumbar punctures and PET scans – are costly and invasive.
The Alzheimer’s Society recently launched a five-year Blood Biomarker Challenge project in the UK in partnership with Alzheimer’s Research UK and the National Institute of Health and Care Research (NIHCR) to gather the information needed to introduce a blood test for dementia into UK healthcare systems.
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