A blood test for Alzheimer's disease

Researchers in Japan and Australia have just reported results of a new test for early Alzheimer’s disease. This report has caused some excitement in popular media as Alzheimer’s disease is a common and feared affliction in our ageing population. We will explain what this report means.

Currently the only way to be 100 percent certain a person had Alzheimer’s disease is for a pathologist to examine the brain tissue under a microscope after that person’s death. However, there are two other techniques used to test for early and fully-developed Alzheimer’s disease. These are PET scanning and spinal fluid analysis. Both these testing methods have drawbacks. PET scanning requires the person to have an injection of a radioactive tracer that binds to beta-amyloid plaques in the brain. These labelled plaques can then be imaged using a PET scanner to detect the small amount of radioactive emissions from the tracer. PET scanners are not common and expensive to use. The second technique is to take a sample of spinal fluid from the person by doing a lumbar puncture (also called a spinal tap). Beta-amyloid protein can then be measured in the spinal fluid.

Scientists have been trying for a long time to develop tests for beta-amyloid in the blood but this has been very difficult because only tiny amounts of beta-amyloid are present in blood. The scientists in Japan have developed a new very sensitive technique to do these measurements. The new test first concentrates the tiny amounts of beta-amyloid and its fragments by a technique called immunoprecipitation. Once concentrated then another highly advanced analytical method called mass spectrometry is used to measure the amounts of the various fragments of beta-amyloid present.

The scientists compared the results of their tests to PET scanning and spinal fluid analysis in two independent groups of people, one group of 121 in Japan and a separate group of 252 people in Australia. Both groups included people who had normal brain function, people with mild cognitive impairment and patients with Alzheimer’s disease. They found that using ratios of some of the different beta-amyloid fragments they measured in the blood samples allowed them to get a good correlation with the amount of amyloid plaques in the person’s brain as measured by PET scanning and spinal fluid analysis.

What is the significance of this new test? The immediate potential for the new test is going to be for clinical trials. Scientists in drug companies and universities are looking for drugs that can delay or prevent the development of Alzheimer’s disease. It is very likely that any drugs found will be most effective if used in the very earliest stages of the disease before the brain accumulates too much damage. Thus, researchers want to recruit people with no symptoms at all or those with the very earliest stages of the disease. Currently such people can only be found by using the expensive or invasive PET and spinal fluid tests. Having a blood test will make it feasible to more easily recruit volunteers for clinical trials.

What about using the test to find out if I am going to develop Alzheimer’s disease? There are two problems here. Firstly, the test has not been validated for this use yet. Only after larger prospective studies following people over many years will we be able to evaluate how accurately the test can predict whether any individual is going to develop Alzheimer’s disease. The second problem is that currently there are no effective strategies or treatments to prevent or treat Alzheimer’s disease. So, if a person gets a positive result on the test, they will know the bad news but also know that there is nothing really effective that they can do about it. Would you really want to know this?

Further Reading
Scientific American
ABC News
Sydney Morning Herald
Nature (news)
Nature (abstract)

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