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expert reaction to biomarker test for Alzheimer’s Disease

A study published in JAMA Neurology looks at Tau immunoassays for Alzheimer’s Disease


Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said:

“This study is a hugely welcome step in the right direction as it shows that blood tests can be just as accurate as more invasive and expensive tests at predicting if someone has features of Alzheimer’s disease in their brain. Furthermore, it suggests results from these tests could be clear enough to not require further follow-up investigations for some people living with Alzheimer’s disease, which could speed up the diagnosis pathway significantly in future. However, we still need to see more research across different communities to understand how effective these blood tests are across everyone who lives with Alzheimer’s disease.  

“Coming down the line are potentially ground-breaking new drugs which can slow the progression of early-stage Alzheimer’s disease, but for people to be eligible for them if they’re approved in the UK, they will need an early, accurate diagnosis. 

“We need to see urgent action to increase dementia diagnosis rates across the UK as many people are in the dark about their condition. That’s why Alzheimer’s Society, along with Alzheimer’s Research UK and the NIHR, hope to revolutionise dementia diagnosis through the Blood Biomarker Challenge. This project – which is thanks to £5m in funding from players of People’s Postcode Lottery – will gather the information needed to introduce a blood test for dementia into UK healthcare systems. This blood test would be a crucial step in speeding up how quickly and how early we are able to diagnose dementia.”  


Dr Mark Dallas, Associate Professor in Cellular Neuroscience, University of Reading, said:

“The search for accurate markers of disease to detect and also predict Alzheimer’s disease will change the way we approach dementia diagnosis and care. The challenges are to find the right marker and one that can be collected routinely with ease. This study looks at changes in blood levels of a unique form of the tau protein (p-tau217), which we know plays a role in driving Alzheimer’s pathology. The results indicate that p-tau217 can track the underlying disease accurately over a prolonged period of time and outperformed other routinely used markers. As new therapies emerge there will be a need to find appropriate markers to select those individuals living with dementia that will benefit the most from access to these drugs, this study starts to provide insight into how we might achieve this.”


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

“People with dementia frequently face unacceptably long delays getting a diagnosis, and with new treatments finally on the horizon, it’s never been more important to transform the way people with potential symptoms of Alzheimer’s are diagnosed. In the past year, we have seen incredible progress in the development of blood-based Alzheimer’s tests. And as we see more and more different types of tests becoming available, studies like this are key to understanding which are most accurate.

“Before any blood tests can become standard diagnostic tools, they must be independently shown to be at least as sensitive and accurate as gold-standard approved tests, such as lumbar punctures. This study suggests that measuring levels of a protein called p-tau217 in the blood could be as accurate as currently used lumbar punctures for detecting the biological hallmarks of Alzheimer’s disease, and superior to a range of other tests currently under development. This adds to a growing body of evidence that this particular test has huge potential to revolutionise diagnosis for people with suspected Alzheimer’s.

“What’s particularly promising about the new study is that the researchers used a cut-off threshold to group people into those who were very likely to have Alzheimer’s, those who were very unlikely to have the disease, and an ‘intermediate’ group who would need further tests using conventional methods like lumbar punctures or PET scans. Using a blood test in this way, the researchers predict, could reduce the demand for these follow-up tests by around 80%.

“However, there are still unanswered questions. We need to gain a better picture of how these types of blood tests perform day-to-day in real-world healthcare systems, including more diverse patient populations. 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 health care setting.

“To try to answer these questions and bring a blood test into routine use within the next five years, Alzheimer’s Research UK is delighted to be working with Alzheimer’s Society and the NIHR on our Blood Biomarker Challenge, thanks to £5 million in funding raised by players of People’s Postcode Lottery. People deserve a quick and accurate diagnosis, which will ultimately bring us closer towards a cure for dementia.”


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

“When effective treatments to prevent the progression of Alzheimer’s disease become available it will be essential to be able to identify people who are at high risk before they begin to deteriorate. This study shows that a simple blood test might be able to do this by measuring levels of tau protein in the blood which has been phosphorylated in a specific way. This could potentially have huge implications. Everybody over 50 could be routinely screened every few years, in much the same way as they are now screened for high cholesterol. It is possible that currently available treatments for Alzheimer’s disease would work better in those diagnosed early in this way. However, I think the real hope is that better treatments can also be developed. The combination of a simple screening test with an effective treatment for Alzheimer’s disease would have a dramatic impact for individuals and for society.”


Prof Charles Marshall, Professor of Clinical Neurology, Queen Mary University of London, said: 

“These findings show that a blood test can accurately detect the presence of the proteins that build up in the brain to cause Alzheimer’s disease. In current practice, the only way to prove that someone has a built-up of these proteins in the brain is to have a lumbar puncture or an amyloid PET scan, which are only available in about 1 in 20 NHS memory clinics. 

“The hope is that blood tests like this will improve access to a diagnosis in those seeking help for memory problems, and ultimately ensure that people can benefit from emerging treatments that can slow the progression of Alzheimer’s disease. Before these tests become widely used in the NHS, we will need further evidence to show that the blood test can accurately diagnose who is in the process of developing dementia, and that it can identify who is likely to benefit from treatments to slow down the disease. We will also need to ensure that the blood test performs equally well in more diverse populations, so that it does not worsen existing health inequalities in access to diagnosis and treatment for dementia.” 


Prof Bart De Strooper, Professor of Alzheimer’s Disease research at UCL, said: 

“This is an excellent study and brings us very close to a blood test for Alzheimer’s disease that can be used in daily practice.” 


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 is a strong study from Dr Ashton and colleagues at the University of Gothenburg showing promising data for a blood test that detects one of the pathological proteins that clumps in the brains of people with Alzheimer’s disease.  The blood test detects tau protein that is phosphorylated at a specific site (the amino acid threonine at position 217 in the protein).  Previous work has demonstrated that high levels of this “p-tau 217” in blood are found in people with Alzheimer’s pathology in the brain.  These tests have only been used for research purposes, not in routine medical practice. This study extended the previous data using a commercially available test, which is a step closer to being able to use these blood tests in clinical practice.  This is important because new drugs to treat Alzheimer’s are coming to the market and already approved in the US, which work best in people in early stages of Alzheimer’s.  Blood test that can help detect people in early stages of disease will be very important for early diagnosis and use of the new treatments in future.  It is important to note that even though the test in this study was very accurate in predicting whether a person has Alzheimer’s disease  pathology in their brain,  not everyone with these pathologies will go on to develop Alzheimer’s dementia.” 


Prof Jonathan M Schott, Professor of Neurology, MRC Investigator, Dementia Research Centre, UCL Queen Square Institute of Neurology, said:  

“An accurate diagnosis of Alzheimer’s disease is already important and will become vital as we enter an era of disease modifying therapies. The current means of acquiring a molecular diagnosis – CSF examination or PET imaging – are costly, invasive, and available only to a fraction of patients. This comprehensive high-quality study shows that a commercially available plasma p-tau 217 assay is as accurate as CSF at detecting key aspects of Alzheimer pathology. Important for its use in clinical practice, the authors confirm that applying a previously proposed two-cut-point model they were able to determine the presence or absence of AD pathology with high certainty, reducing the numbers who might need further investigation (CSF/PET) by ~20%. This vitally important work paves the way for studies assessing the utility of plasma p-tau 217 in routine memory clinics and in diverse populations – if these findings are replicated in real-world clinical settings, plasma p-tau 271 has the potential to revolutionise the diagnosis of AD.” 



‘Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology’ by Nicholas J. Ashton et al. was published in JAMA Neurology at 16:00 UK time on Monday 22nd January 2024/


DOI: 10.1001/jamaneurol.2023.5319 



Declared interests 

Prof De Strooper: none with the current work, but I am a colleague of Dr. Henrik Zetterberg in the UK-DRI.  

Prof David Curtis: I have no conflict of interest.

Dr Mark Dallas: Nothing to declare.

Prof Charles Marshall: No conflicts.  

Prof Schott undertakes plasma biomarkers studies in AD, and collaborates with the lead authors of this study. 

For all other experts, no reply to our request for DOIs was received. 


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