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AAIC 2023 | DROP-AD: detecting Alzheimer’s disease biomarkers in a single blood spot
Hanna Huber, PhD, University of Gothenburg, Mölndal, Sweden, and Nicholas Ashton, PhD, University of Gothenburg, Mölndal, Sweden & King’s College London, London, UK, discuss their pilot study investigating the capability of a finger prick collection method for detecting blood-based biomarkers of neurodegeneration. DROP-AD enrolled 43 participants who underwent blood collection from a finger prick (capillary dry blood spot) and venous puncture (venous dry blood spot). The samples were spotted and dried onto cards, before being shipped overnight without temperature control. Analysis of the samples showed a strong correlation between biomarker levels (GFAP, NfL, and p-tau217) from the capillary and venous dry blood spots, both of which also correlated with EDTA plasma levels. Notably, there was a significant difference in blood spot biomarker levels between individuals classified as amyloid positive versus negative by PET imaging. Dr Ashton highlights the benefits of a simple finger prick collection method, which has the potential to enable at-home, regular monitoring in a quick and easy fashion. This interview took place at the Alzheimer’s Association International Conference® (AAIC) 2023 in Amsterdam, Netherlands.
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Transcript (edited for clarity)
The project is called DROP-AD and the idea is that we want to have a simpler method in order to detect Alzheimer’s disease biomarkers. So, a lot of this conference has been about phosphorylated-tau and neurofilament light and GFAP and how important they’re going to be in the future of diagnostics, particularly when we have a new drug which could potentially lower amyloid and has clinical benefit...
The project is called DROP-AD and the idea is that we want to have a simpler method in order to detect Alzheimer’s disease biomarkers. So, a lot of this conference has been about phosphorylated-tau and neurofilament light and GFAP and how important they’re going to be in the future of diagnostics, particularly when we have a new drug which could potentially lower amyloid and has clinical benefit. Now we recognize that there are maybe some potential issues with blood collection, the fact being that in primary care we’re not set up quite yet to collect blood in the way that we need it. We want to be able to monitor patients more regularly over time for personalized management. So, the way that DROP-AD is trying to serve that area by having a simpler method to collect blood from patients and do the same diagnostic tests, but on a on a method which can be collected remotely or in primary care.
We did a study in at the Alzheimer’s Center in Barcelona where the study team collected blood samples from venipuncture but also from finger prick and they spotted the capillary and the venous blood onto a card and then they shipped the card to the University of Gothenburg, where we extracted the cards and analyzed the elution and measured the biomarkers that are related to Alzheimer’s disease and we also measured as a reference the plasma values of those biomarkers because as they are the reference that we are using for blood based biomarkers. And then we correlated the results from the finger prick samples and the venous samples from the card with the plasma biomarkers and we found that they correlate quite strongly and significantly. Then we also distinguished the patients from the memory clinic regarding the amyloid status, so if they are amyloid positive or amyloid negative in their CSF values, and there we also saw that the capillary and the venous samples or concentrations in the samples differ significantly between the groups. So it seems like we can also use capillary, for example, phospho-217 to distinguish amyloid positive and amyloid negative individuals.
Yeah. So I mean, the essentially the punchline of the experiment is that we essentially can come up with a similar result from a finger prick test that you can with a standard blood tests which everyone are rightly assuming are the new gold standard in AD diagnostics. The study is preliminary. There are several different questions that we need to answer. Stability of the blood on the blood spot cards. Can it withstand going in the post or staying in a doctor’s office or those type of things? And really where you want this is potentially in the many, many years is individuals being able to collect blood spots by themselves and it being analyzed in the lab and the variability of individuals being able to do that themselves when they don’t have a research nurse to help them with it. What kind of variability do we see there? But the preliminary results are super encouraging that we can say that essentially, first of all, we were quite surprised that we could measure phosphorylated tau in the finger prick test for a start and that it relates to the blood EDTA normal blood measures of this biomarker. I think it’s super encouraging.
So there are multiple things we have to think about. The stability question is the major one and we started to answer this. You know, how many weeks can we still use this blood test for in the extraction process? We need to also understand the extraction process. You know, it has it has some steps to it, right? So we need to make sure that that is a stable measurement over time. I think that this is something which people can really easily get on board with. You know, this is a lot of people do finger-pricks for multiple different tests around for different disorders. So we see that this is potentially an application for primary care if we can prove it in larger cohorts, as you say, a potential for home collection as a pre-screening tool. Maybe if you’re at risk, maybe someone has subjectively concerned for their cognitive health, it could be kind of an entry point for you then getting a more specific test by going to see a doctor that way.
So the plan with this, as I say, this is a preliminary study. We know that the biomarker levels from the finger prick and the plasma correlate. What we need to now test is that the diagnostic accuracy is also the same. This is something we haven’t done extensively. So we’re working with several centers around Europe where they will start prospectively collecting the finger prick test, the venous blood test and the EDTA test and will test this kind of in a head to head fashion. And then the next step, if that’s positive, is what we’ve discussed, is being able to test this application of people collecting finger-prick test unsupervised. So can they do this themselves? Do you get the same results as if you did it with a nurse helping you out at the same time? So that would kind of prove the feasibility of it.