With further study, this research may provide clinical laboratories with a new proteomic biomarker for dementia screenings that identifies risk more than 10 years before symptoms appear
Researchers at the University of Warwick in the UK and Fudan University in Shanghai, China, identified four protein biomarkers in blood that they say can predict dementia up to 15 years before diagnosis. They say these biomarkers may lead to clinical laboratory blood tests that offer alternatives to costly brain scans and lumbar punctures for diagnosis of dementia.
The scientists “used the largest cohort of blood proteomics and dementia to date,” according to a University of Warwick news release. This included taking blood from 52,645 “healthy” people without dementia who participated in the UK Biobank—a population-based study cohort, the new release noted.
“The proteomic biomarkers are [easy] to access and non-invasive, and they can substantially facilitate the application of large-scale population screening,” said neurovegetative disease specialist Jin-tai Yu, MD, PhD, a professor at Fudan University and co-author of the study, in the news release.
The scientists published their findings in the journal Nature Aging titled, “Plasma Proteomic Profiles Predict Future Dementia in Healthy Adults.”
“The advent of proteomics offers an unprecedented opportunity to predict dementia onset,” the researchers wrote.
“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,” said Tara Spires-Jones, PhD, in a post from the Science Media Center in the UK. “However,” she added, “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.
Jones, who was not involved in the study, is President of the British Neuroscience Association (BNA) and group leader of the UK Dementia Research Institute at the University of Edinburgh.
“Based on this study, it does seem likely that blood tests will be developed that can predict risk for developing dementia over the next 10 years, although individuals at higher risk often have difficulty knowing how to respond,” Suzanne Schindler, MD, PhD (above), told Reuters. Schindler, an Associate Professor of Neurology at Washington University in St. Louis, was not involved in the research. Clinical laboratories may soon have a new blood test for dementia. (Photo copyright: VJDementia.)
Predicting Onset of Dementia with 90% Accuracy
The researchers analyzed 52,645 blood samples from the UK Biobank (UKBB). The samples were collected between 2006 and 2010 from healthy individuals who at that time were without dementia.
By March 2023, 1,417 of the study participants had developed Alzheimer’s disease or some other form of dementia. The researchers looked at 1,463 proteins and identified four that were present in high levels among those people:
- Glial fibrillary acidic protein (GFAP),
- Neurofilament light (NEFL),
- Growth differentiation factor-15 (GDF15), and
- Latent-transforming growth factor beta-binding protein 2 (LTBP2).
“Individuals with higher GFAP levels were 2.32 times more likely to develop dementia,” the researchers wrote in Nature Aging. “Notably, GFAP and LTBP2 were highly specific for dementia prediction. GFAP and NEFL began to change at least 10 years before dementia diagnosis.”
When adding known risk factors such as age, sex, and genetics, the researchers said they could predict onset of dementia with 90% accuracy, according to the University of Warwick news release.
“Our findings strongly highlight GFAP 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,” the researchers wrote.
The news release also noted that smaller studies had already identified some of the proteins as potential biomarkers, “but this new research was much larger and conducted over several years.”
Further Validation Needed
Amanda Heslegrave, PhD, of the UK Dementia Research Institute, University College London described the UKBB as “an excellent resource” in the Science Media Center (SMC) post. However, she noted, it’s “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.”
Another expert raised additional questions about the University of Warwick/Fudan University study in the SMC post.
“These results may help researchers understand the biological systems involved in the development of dementia,” said David Curtis, MD, PhD, of the UCL Genetics Institute at University College London. “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.”
Conversely, Curtis pointed to other studies suggesting that phosphorylated tau (p-tau) proteins are better candidates for developing a simple blood test.
P-tau “provides a very good indicator of whether the pathological processes leading to Alzheimer’s disease are present in the brain,” he said. “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.”
At least two blood tests based on the p-tau217 variant—from ALZpath and C2N—are currently available to US clinicians as laboratory developed tests (LDT).
In “University of Gothenburg Study Findings Affirm Accuracy of Clinical Laboratory Blood Test to Diagnose Alzheimer’s Disease,” Dark Daily reported on a study from the University of Gothenburg in Sweden which found that the ALZpath test was as good or better than lumbar punctures and brain scans as a diagnostic tool for Alzheimer’s.
UK Biobank
The UK Biobank continues to be used by researchers both in the UK and abroad because of the full sets of data on large numbers of patients over many years. There are few other sources of such data elsewhere in the world. The UK Biobank is a large-scale biomedical database and research resource. It contains de-identified genetic, lifestyle and health information, and biological samples from 500,000 UK participants.
On its website, the UK Biobank states, “It is the most comprehensive and widely-used dataset of its kind and is globally accessible to approved researchers who are undertaking health-related research that is in the public interest, whether they are from academic, commercial, government or charitable settings.”
Thus, clinical laboratory managers and pathologists can expect a continuing stream of published studies that identify biomarkers associated with different health conditions and to see where the data used in these analyses came from the UK’s biobank.
—Stephen Beale
Related Information:
Protein Biomarkers Predict Dementia 15 Years Before Diagnosis, According to New Study
Plasma Proteomic Profiles Predict Future Dementia in Healthy Adults
Proteins May Predict Who Will Get Dementia 10 Years Later, Study Finds
Expert Reaction to Study of Potential Protein Biomarkers for Dementia Risk
Two New p-Tau217 Blood Tests Join a Crowded Field
Plasma p-Tau-217 Assays Work Well, But No Home Run for Diagnosis
Dementia Can Be Predicted More than a Decade Before Diagnosis with These Blood Proteins
Dementia Predicted 10 Years Before Diagnosis
Early Blood Test to Predict Dementia Is Step Closer as Biological Markers Identified
Validating Blood Tests as A Possible Routine Diagnostic Assay of Alzheimer’s Disease