Discovery of blood-based ‘signature’ for Alzheimer’s disease could accelerate search for treatment

Researchers have identified a chemical signature in the blood which is linked to the build-up of harmful plaques in the brain that lead to Alzheimer’s disease.  The findings could help to accelerate the search for an effective treatment for the condition, by allowing more streamlined clinical trials.

While Alzheimer’s disease can only be definitively diagnosed after death, certain changes which occur in the brain of people with the condition can be detected during a person’s lifetime, allowing researchers to differentiate Alzheimer’s disease from other types of dementia. 

The two most important indicators of Alzheimer’s disease in the brain are characteristic tangles of proteins, and clumps (plaques) of another kind of protein called beta-amyloid.  While build-up of these features in the brain is a characteristic sign of Alzheimer’s disease, they are difficult to measure directly, requiring complicated and expensive brain imaging, which is why researchers are searching for simpler correlates of these structures – referred to as biomarkers – which can be more easily measured.

According to Nicola Voyle, one of the study’s lead authors from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at Kings College London, “Existing research suggests that some potentially promising therapies for Alzheimer’s disease may work best on patients with high levels of amyloid plaques, but the difficulty and expense of testing this in patients using brain imaging means that identifying these patients is rarely feasible.”

BRC/U researchers focused on several chemicals in the blood which have previously been associated with an increased risk of Alzheimer’s disease.  The chemicals, referred to collectively as blood metabolites, can be easily measured through blood tests, but their relation to the brain biomarkers of Alzheimer’s disease was unknown.

The researchers assessed the level of these blood metabolites in a group of 91 people with Alzheimer’s disease enrolled in the University of California, San Francisco, Alzheimer’s Disease Research Centre.  Using sophisticated data analysis techniques, they then used brain imaging data from the same group to assess whether there was any connection between the blood metabolites and a high level of amyloid plaques.

They found that a chemical ‘signature’ of five blood metabolites was able to identify patients with high levels of amyloid plaques with 72% accuracy.  When a protein, fibrinogen, was added to the signature, accuracy improved to 79%.  This is enough to allow researchers running clinical trials to more accurately select which individuals should be further tested using brain scans, potentially saving considerable time and expense, and minimising the number of patients with low levels of plaques participating in trials of unsuitable therapies.

“If our findings are replicated in larger studies, we should ultimately be able to develop a simple blood test to identify patients with high levels of amyloid plaques, which could lead to better stratification in clinical trials of potential therapies, and eventually raises the possibility of personalised treatment for patients with high levels of amyloid plaques,” said Dr Richard Dobson from IoPPN, another of the study’s lead authors.

The study was relatively small, which means that the next step is for the results to be tested in a larger population.  The mechanisms by which the blood metabolites are related to amyloid plaque build-up are also unknown, so further research into why this particular pattern of metabolites appears in the blood of patients with high levels of amyloid plaques could also lead to further insights into the development and progression of Alzheimer’s disease.”

The research is published in the journal Translational Psychiatry, and was part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. The research leading to these results received support from the Innovative Medicines Initiative Joint Undertaking (European Medical Information Framework – Alzheimer’s Disease), and some of the researchers were supported by the MRC and the Alzheimer’s Society.