February 12, 2024

expert reaction to study of potential protein biomarkers for dementia risk

A study published in Nature Aging looks at possible plasma protein biomarkers for dementia risk. 

Dr Sheona Scales, Director of Research at Alzheimer’s Research UK says:

“We have seen some fantastic progress in the development of blood tests for Alzheimer’s over the last few months.

“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.

“Using over 50,000 samples from the UK Biobank, which holds genetic, lifestyle and health information along with biological samples, researchers looked at how levels of 1,463 proteins in the blood changed over 14 years. They were able to identify a number of proteins whose levels began to vary a number of years before people were diagnosed.

“Further studies, including in more diverse populations, are needed to verify these tests and predictive models. And, 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.

“Finding better, more accessible ways to diagnose dementia is crucial. 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. New treatments like lecanemab, should they be approved, will only be effective if they are given to people in their early stages of Alzheimer’s, and at the moment very few people have access to the specialist tests that would be needed.

“Blood tests could unlock early diagnosis and are showing great promise, but so far, none have been validated for use in the UK. In collaboration with Alzheimer’s Society, NIHR, and with generous funding from players of People’s Postcode Lottery, we are in the process of funding research to provide the evidence the NHS would need to move forward with blood tests to diagnose Alzheimer’s disease”.

Prof 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 paper by Guo and colleagues looked at data from blood samples of over 50,000 people participating in the UK Biobank study. The scientists found that high levels of several proteins in blood were associated with developing dementia. This is a well-conducted study that adds to what we know about changes in blood that occur very early in diseases that cause dementia, which will be important for early diagnosis in the future.  However, it is important to note that these are still scientific research studies and that there are currently no blood tests available for routine use that can diagnose dementia with certainty.”

Prof David Curtis, Honorary Professor, UCL Genetics Institute, University College London (UCL), said:

“This paper reports that levels of some proteins in the blood tend to differ in people who will later be given a formal diagnosis of dementia. These results may help researchers understand the biological systems involved in the development of dementia. However in my view the strengths of 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.

“I would contrast this with the recent reports that measuring phosphorylated tau protein in the blood provides a very good indicator of whether the pathological processes leading to Alzheimer’s disease are present in the brain. When effective treatments for Alzheimer’s disease are developed it will be very helpful indeed to have simple blood tests, such as measuring phosphorylated tau, available in order to identify who could benefit.”

Dr Amanda Heslegrave,  Senior Research Fellow at the UK Dementia Research Institute, University College London, said:

“This study looks at a very large cohort from the UK Biobank, over 50k subjects without dementia with samples available for a long follow up period – this, coupled with information about dementia outcomes enables a study that examines changes in proteins in blood and how these are different between people who go on to be diagnosed with dementia and those who don’t – this then enables risk to be predicted – studies such as this are required if we are to intervene with disease modifying therapies at the very earliest stage of dementia. – the press release does reflect the science.

“This research utilised an excellent resource in UK biobank and a respected technology – the findings appear robust given the knowledge we already have about GFAP being highly associated with AD and NfL not being specific for any one dementia – the message to take away here is that for accurate diagnosis and differentiation between dementias we need focused panels of biomarkers.

“Limitations to be aware of are that the UKBB is a highly curated biobank and may not capture all populations that we need to know the risk for – the new biomarkers identified will need further validation before being used as screening tools.

“The implications are that with disease modifying treatments close to being approved in the UK we need to develop a screening strategy, this study with its use of follow up data needs to be replicated and biomarkers that enable us not only to screen for disease risk but also to differentiate between diseases should be a priority.”

‘Plasma proteomic profiles predict future dementia in healthy adults’ by Guo et al. was published in Nature Aging at 16:00 UK time on Monday 12^th February.

DOI: 10.1038/s43587-023-00565-0

Declared interests

Dr Sheona Scales: Nothing to declare

Prof Tara Spires Jones: I have no conflicts with this study.

Prof David Curtis: I have no conflict of interest.

Dr Amanda Heslegrave: No COIs to declare