Alzheimer's disease, believe it or not, is very hard to diagnose definitively because it relies on seeing particular pathology in the brain when you look with a microscope. The pathology is the accumulation of a protein called amyloid and another protein called tau around the nerves. This makes testing treatments hard, as well as predicting the future for families and individuals who are having thinking and memory problems. The holy grail was a blood test, also called a biomarker, and that's what Alexis Moscoso has been working on at the University of Gothenburg in Sweden.
Alexis Moscoso: We now know that biomarkers are necessary because the clinical diagnosis is not accurate enough to detect Alzheimer's disease. A patient might have a clinical syndrome that is perfectly compatible with what we understand as Alzheimer's disease, you know, memory loss and all these cognitive deficits, but in fact might be another disease. So that's why we need biomarkers to see what's going on in the brain and detect the pathological hallmarks of Alzheimer's disease.
Norman Swan: It's a fancy name, biomarkers. We use biomarkers all the time, so for a heart attack there is a biomarker called troponin, for high cholesterol there is a biomarker there which is your cholesterol test. This is just another blood test. So what is this particular blood test measuring that you've been looking at?
Alexis Moscoso: This particular blood test is measuring one of the pathological hallmarks of Alzheimer's disease which is the abnormal aggregation of the tau protein. Alzheimer's disease is characterised by two proteinopathies, one is amyloid pathology and the second is tau pathology. So with these blood tests we are measuring very accurately the presence of tau pathology in the brain.
Norman Swan: And just to explain, when you look at the brain under the microscope, which of course you can't do in people in life, these two proteins gather around the nerves, the amyloid and the tau. And what you are looking at presumably is a spill-over into the blood of the tau protein.
Alexis Moscoso: We don't understand yet how exactly these tau proteins finally get to the bloodstream. What we know is that these blood-based biomarkers are really promising and they perform really well.
Norman Swan: So what did you do in this study?
Alexis Moscoso: In this study what we did is basically to study how these new plasma biomarkers are able to predict future neurodegeneration and cognitive decline.
Norman Swan: And just to explain, the group of people you are looking at are a group of people you've been following, you've been doing brain scans on them, including PET scans, which are very fancy imaging scans of the brain, looking at how the brain is metabolising, as well as following how they are going functionally. And what did you find? How close was the tally, if you like, between the tau in the blood and the progression of some of these people to Alzheimer's and indeed worse functioning?
Alexis Moscoso: First of all we found that plasma phospho tau was able to predict progressive neurodegeneration and cognitive decline in the future, both in initially cognitively impaired individuals, individuals experiencing symptoms of the disease, but most importantly in individuals who were cognitively unimpaired, who were cognitively healthy. This is one of the most important results of our study.
And the other important result was that, yes, these progressive neurodegenerative changes and progressive cognitive decline were accompanied by an increase in the levels of plasma phospho tau in blood. So plasma phospho tau might be helpful to predict and monitor disease progression.
Norman Swan: Given that you found it in the blood of people who were yet to develop dementia and cognitive decline, is this a diagnostic marker? In other words, if you did this test and it was positive, can you say this person has Alzheimer's disease?
Alexis Moscoso: There is an ongoing discussion that Alzheimer's disease should be considered a purely biological entity. This means that one individual can have Alzheimer's disease without experiencing any type of symptoms. The only requirement to have Alzheimer's disease is positive test of amyloid and a positive test of tau. And we now know that plasma phospho tau is a relatively good marker of both amyloid and tau pathology. So yes, with reasonable accuracy we can detect these two hallmark pathologies of Alzheimer's disease in living brains.
Norman Swan: And what you're referring to there is the work particularly of Karen Ritchie, an expatriate Australian in the south of France who is showing that you can have indications of Alzheimer's disease when you are entirely normal, maybe 20 years, 30 years before dementia develops. What's the use of knowing this when we don't have treatments?
Alexis Moscoso: It's important because we need to identify individuals who are having Alzheimer's disease who actually have the pathology we are targeting with treatments. That was a major limitation of previous clinical trials. For instance, we are including subjects with the clinical syndrome of Alzheimer's disease, but about 30% of them did not have Alzheimer's disease at all. So if you are testing a disease modifying drug that is targeting Alzheimer's disease pathology and you are including subjects without Alzheimer's disease, the trial is not going to be as effective as it could be, that's why it's so important, the use of biomarkers and knowing that someone has the pathological hallmarks of the disease.
It's also important to know that both who are cognitively unimpaired and has both amyloid and tau pathology in the brain, as measured with PET, for instance, with positron emission tomography, cerebrospinal fluid biomarkers or even now with plasma phospho tau, will have likely cognitive decline in the next coming years. So we can anticipate the families and the caregivers to what's going to happen in the next few years. So even though we don't have treatments yet, I think it's very relevant for clinicians to achieve an accurate diagnosis with the use of biomarkers.
Norman Swan: And just finally, is this a test that is accurate and able to be scaled up to commercial pathology labs so that general practitioners one day might be able to order it, and is it affordable?
Alexis Moscoso: That's the main strength of this plasma biomarker because we can now measure amyloid and tau with a positron emission tomography machine. The problem is that this is a very expensive technique, and it's only limited to very specialised centres. With cerebrospinal fluid biomarkers there is a similar problem, it is a relatively invasive technique because it requires a lumbar puncture. But with plasma biomarkers, they are both cheap and minimally invasive, so this is the biomarker that we were looking for.
Norman Swan: Thank you very much indeed for joining us.
Alexis Moscoso: Thank you very much for having me.
Norman Swan: Dr Alexis Moscoso is in the Department of Psychiatry and Neurochemistry at the University of Gothenburg in Sweden.
Alzheimer's disease is hard to diagnose definitively because it relies on seeing particular pathology in the brain - a collection of a protein called amyloid and another called tau around the nerves. This makes it difficult to test treatments, and to predict the future for people with thinking and memory problems.
Guest:
Dr Alexis Moscoso
Post-doctoral Researcher,
University of Gothenberg
Host:
Dr Norman Swan
Producer:
Diane Dean