In the blood

Potential blood tests for Alzheimer's disease get a lot of attention from patients, families, researchers and the media. We take a closer look at why blood tests are so popular and where they could start to make a difference.

Developing a blood test for Alzheimer's disease is a hot topic in dementia research and hardly a month goes by without another story appearing in the news. These tests are getting more and more accurate, but what are they and what can they be used for?

Why blood?

Currently, the only way to fully understand the biochemical changes in someone with dementia is to take brain samples after death. It is not feasible or desirable to carry out surgery to get brain samples in order to get a diagnosis and predict the progression of the disease. All that doctors can do now is to use imaging technology, such as PET scans, that allow them to see the build-up of proteins in the brain.

'The primary reason for focusing on blood is that, compared to other tissues, it's quite easy to access.'

says Dr Richard Dobson, a researcher at King's College London.

'And it can be lower cost, relatively, to screen for signatures in the blood than through a PET imaging scan.'

As the blood circulates it picks up proteins and other chemicals from different parts of the body. This means that blood samples can say a lot about what's happening inside us – that is, if we know what to look for.

Lots of choice

There is a lot of research currently trying to find markers of dementia in blood. Several new blood tests have received a lot of publicity in the past year. They are all looking for subtle changes to chemicals in the blood that are linked to Alzheimer's disease, but come in several different varieties.

In March 2014, a team from Georgetown University published the results of a blood test that predicted Alzheimer's disease in a small group of people with 90 per cent accuracy by identifying 10 different fat molecules that were linked with the condition.

Then in May, researchers announced another blood test that worked by searching for proteins. This study involved many more participants and had an accuracy of 87 per cent, but only for the progression from mild cognitive impairment to Alzheimer's disease. A couple of months ago, researchers in Australia developed a test that studied small molecules known as micro RNA. These molecules help to control the activities of cells and could be used to predict dementia years in advance with 91 per cent accuracy.

These results sound promising but they might still be some way from being reliable enough to be used more widely.

'Most of these markers are at the validation and replication stage.'

says Dobson.

'We have to think about them in the context of normal ageing changes and other disease changes. We have to be careful about how specific these signals that we’re identifying are for Alzheimer's and dementia.

'At the moment we're just looking at one aspect: we're looking at the RNA or at proteins or at metabolites. One great thing to do will be to combine these different modalities. The technology is there now to generate this data.'

Power of screening

An accuracy of 90 per cent might sound good enough for a test to diagnose people, but in reality it is still far too low. Most people do not develop dementia and this means there would be far too many people given false diagnoses, with damaging consequences.

Although these tests have a long way to go before they could be used for diagnosis, they could be useful in recruiting people for clinical trials to test new drugs. Scientists suspect that to find new drugs for Alzheimer's disease they will have to try them in people at a very early stage in the disease – potentially even before symptoms appear.

Dobson explains:

'Drug trials have more chance of succeeding if you can identify people in this preclinical stage. That's why we're interested in finding blood markers of these brain changes.

'That's where you've got real potential to slow down disease progression before too much damage is done.'

We already know that there are changes in the body's chemistry long before the signs of dementia appear. The key is spotting these changes in a way that is reliable. With current technologies, this requires PET imaging scans of healthy people and looking for signs that Alzheimer's disease will develop. However these signs might only exist for one in 10 of study participants, meaning that perhaps 1,000 volunteers would need to be screened in order to recruit 100 suitable people for a trial.

Dobson says this just isn't sustainable.

'You have a really high failure rate in identifying people suitable for the clinical trial and it's very expensive.'

This is where even an imperfect blood test could be useful.

'Even if the blood marker isn't that amazing, say 80 or 90 per cent, it doesn't have to be. Even if it was just like a coin toss, that greatly reduces the number of people you have to scan.'

This is why the focus for a lot of blood test research is to help clinical trials. If drug trial recruitment can be improved, then it might turn around the string of failures we have seen over the past decade. Being able to intervene earlier could be crucial in delaying the development of dementia or preventing it completely.

Looking ahead

Improving clinical trial recruitment might not sound ambitious, but it could have a big impact within just a few years. And that’s not all that blood tests can do. There is research into providing a definitive diagnosis of dementia, predicting the progression of the disease and telling the difference between forms of dementia.

These tests might not be ready just yet, but in the meantime blood tests are likely to keep appearing in the media and getting public attention.