An Alzheimer’s blood test could also help develop new drugs

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US scientists recently announced they had developed a blood test that could predict your chances of developing Alzheimer’s disease, with 90% accuracy, up to three years in advance of other known symptoms.

The scientists from Georgetown University in Washington DC and University of Rochester School of Medicine, New York, did this by analysing the blood of 53 people who went on to develop Alzheimer’s or mild cognitive impairment from a study group of 525 people older than 70, compared to another 53 who didn’t. The difference in the levels of ten fats (phospholipids) in the blood of the two groups at the beginning of the study provided a predictive test of those at risk of developing either mild cognitive impairment or Alzheimer’s disease.

There are more than 800,000 people in the UK estimated to be living with dementia. More than half of these have Alzheimer’s disease, the most common cause of dementia. The cost of these diseases to the UK economy stands at £23 billion, more than the cost of cancer and heart disease combined. With the ageing demographic of the population, lack of a treatment for the underlying cause of the disease is a growing public issue.

The development of Alzheimer’s disease can proceed silently for up to a decade or more before any symptoms emerge and a key bottleneck in the development of treatments is the urgent need for much earlier diagnosis, before memory loss is evident and the disease becomes entrenched. Finding “biomarkers” like those identified by the US scientists in the blood samples could allow diagnosis to be made before clinical signs are first seen.

The fats, or phospholipids, are an important part of cell membranes, and levels in the blood are thought to reflect changes to the integrity of membranes that might happen during early neurodegeneration. Blood biomarkers are likely to provide one of the most cost effective diagnostic tools, but have so far proved elusive. Other methods are expensive, such as brain imaging, or invasive for the patient, for example spinal fluid samples.

The problem with current treatments is that they only help to alleviate symptoms, so a number of new treatments being developed aim to go further by slowing or stopping the underlying mechanisms. In the Institute of Integrative Biology at Liverpool University, we have been developing chemically synthesised compounds based on natural sugars, which strongly inhibit the action of an enzyme called beta-secretase. This enzyme is responsible for generating the small peptides made of amino acids that accumulate in clumps, or plaques, in the brains of people affected with Alzheimer’s. Targeting these plaques has been identified by drug companies as a key way to treat the disease, but it has proved difficult to inhibit this enzyme with classic small molecule drugs.

Successful development of drugs that have prevent or break down these plaques could result in disease-modifying therapies to slow or even halt progression of the disease.

Better early diagnosis could lead to advances in the development of disease-modifying drugs, which could be given to patients earlier, boosting their chances. Some promising drugs in clinical trials may have failed to produce any real benefit for the patients because they were given too late in the disease process. Testing such drugs at an earlier stage may reveal hitherto unseen benefits.

The blood changes discovered by Howard Federoff and his colleagues in the US study may provide a sensitive measure of early neurodegenerative events, and this could also provide a way of selecting groups of patients suitable for trialing new drugs.

It’s a combined front and still early days – the blood test, for example, still needs to be tested in a much larger clinical trial. The phospholipids may also provide clues for finding new biomarkers to improve the accuracy of testing. They might also permit even earlier diagnosis beyond the current three-year lead time the team describe. Extending their study to a much larger group of patients is the next step. If the data holds up this should lead to new opportunities to advance the development of new drugs in early treatment trials.