New biomarkers for Alzheimers?

Are there any better diagnostic tests, or biomarkers, that could help with early diagnosis of Alzheimer's and prevent tau tangles accumulating. Simon Lovestone is based at Oxford University...

Simon -   So, I work on what are called biomarkers - essentially, tests for Alzheimer's disease.  What I'm really interested in is not so much a test for Alzheimer's disease, but can we find a way of identifying people who are going to develop Alzheimer's disease.

Hannah -   What's the hope in the future?  What's a realistic timescale in terms of being able to diagnose and treat Alzheimer's before the proper brain damage, in effect to actually set in?

Simon -   So currently today, when people come to their doctor for the first time, worried they have Alzheimer's disease, what we actually do is do some memory tests.  Often, we can't tell whether somebody has got Alzheimer's disease.  So, what we then do is say, "Come back and see us in 6 months or a year and if it's got worse, we'll tell you whether it's got worse due to Alzheimer's disease or not."  That's a terrible 6 months or a year for patients, not knowing what's happening, waiting for the results, terrible anxiety.  So even though we have no treatments today, the way we have of diagnosing Alzheimer's disease is just not adequate.  Using biomarkers today, using a lumbar puncture - that's a needle into the base of the spine to get spinal fluid or using some very complicated test, neuroimaging of the brain, we can actually diagnose Alzheimer's disease quicker today, using biomarkers.  I think we should start doing more of that.

Hannah -   Why is it that that isn't being implemented that commonly now?  Is it cost?

Simon -   I don't think it's just cost that prevents us from implementing that.  I think it's logistically difficult.  I think it's uncomfortable, it's invasive.  Some people argue, we don't need that because we don't have any treatments.  I disagree with that view.  But actually, it is beginning to happen.  If you look outside of Britain, in much of Europe and America, it is now becoming more routine to have a spinal fluid test as part of the diagnostic workup.  My prediction is, over the next few years, you'll see a lot of that beginning to happen in the UK as well.

Hannah -   What's different about the spinal fluid in a patient with early stage Alzheimer's compared to a healthy control?

Simon -   So, in Alzheimer's disease, even in the early stage, you can see molecular markers that are indicative of the changes in the brain.  So specifically, you see decreased amount of a protein called A-beta or amyloid.  The reason why it's decreased because it's increased in the brain so there's less of it circulating around.  And you see increased amounts of a protein called tau - phospho tau.  The reason why that's increased is because it's a pathological change that happens in the brain of Alzheimer's disease.  As the neurons die or the brain cells die, it gets released in the spinal fluid.

Hannah -   What type of tests do you think we might have in the future, maybe some less invasive test than a lumbar punch?

Simon -   What we know is that for 10 or 20 years before there are symptoms, there is an accumulation of pathology in the brain.  So, the condition is starting even before there are any clinical symptoms at all.  If only we could treat those people then we might be able to prevent the condition.  At the moment, we can't treat those people because we don't have the drugs but also, we don't know who those people are.  So, we're trying to develop a test that would enable us to pick up those people before they have symptoms by looking at their blood.

Hannah -   What are you picking up in your blood screening studies so far?

Simon -   So, we've used a method called proteomics.  So, we've been looking at proteins in the blood and we start by looking at a thousand or more proteins.  Over the past 10 years, we've honed down to about 10 or so.  Broadly speaking, these are proteins that have something to do with immunity and the reaction of the body to stress.  That makes sense because we know that the brain is under stress.  We know it has an immune response.  What we're finding is that immune response somehow crosses from what's happening in the brain through to something we can see in the blood.

Hannah -   So, it's almost as though the Alzheimer brain is being attacked by its own immune system.  It's underfire by its own soldiers almost in its defence system and that's what's causing these problems with memory and also delusions and hallucinations 20 years down the line - an attack on our own brain?

Simon -   So, I think that is right.  I think what happens in Alzheimer's disease is that you have a central process if you like, that's the motorway, driving the process of Alzheimer's disease.  We have lots of roads feeding into that, that contribute to that process.  The immune reaction of the brain is one such of those roads that is helping to drive the process along.

Hannah -   How sensitive or selective are your blood diagnostic tests at the moment?  Are you getting some quite promising result?

Simon -   Yes, it's looking very promising indeed.

Hannah -   So, if you took my blood sample now, with what percentage accuracy would you be able to predict that I would be developing Alzheimer's in 20 plus years?

Simon -   Nearly zero because you're way too young.  So, what we're really interested in doing is, can we take somebody who is perhaps 60 or 70 and perhaps has some memory problems already, maybe they have mild cognitive impairment.  What you really want to know is what's going to happen in the next year or two.  That's how we've been designing our studies.  So, we know that our test is quite accurate in detecting people with mild cognitive impairment and predicting what's going to happen to them in the next 18 months.

Hannah -   Promising research.  Thanks to Simon Lovestone from Oxford University.  Well, I'm afraid that's all we have time for this month. 

Thanks to Alzheimer's Research UK for this special podcast, reporting from their conference and featuring Susie Hewer, John Gallagher, Karen Richie, Kevin Morgan, Eric Karran, and Simon Lovestone.  To find out more about the disease, please visit the website worldwideweb.alzheimersresearchuk.org. 

We'll be back again next month to open our minds.  The topic for the next show is autistic spectrum disorder.  Could environmental pollutants play a role?  Is it simply extreme male behaviours?  Can you diagnose newly born babies and start treating?  We'll find out.  If you have any comments or questions, please contact Hannah@thenakedscientists.com, you can also tweet @nakedscientists, or you can post on the Naked Scientists Facebook page.  You can find the full transcript for this episode and others on our website.  It's thenakedscientists.com/neuroscience.  See you next month to open our minds.