Viewpoint: Alzheimer’s diagnosis advance is a significant step towards improved treatments

Professor Jerry Turnbull is Johnston Professor of Biochemistry in the University of Liverpool’s Institute of Integrative Biology

“A key bottleneck in the development of treatments for Alzheimer’s disease (AD) is the urgent need for much earlier diagnosis, before memory loss is evident and the disease becomes entrenched.  Recent research has discovered just such a panel of “biomarkers” in blood samples that allow diagnosis of AD up to 3 years before clinical signs are normally observed.

“The research, reported in the journal Nature Medicine, was led by Prof Federoff from the Georgetown University Medical Center in Washington DC in USA. The team discovered that measuring a panel of 10 specialised fats called phospholipids in blood samples provided a test with 90% accuracy to predict the onset of mild cognitive impairment or AD up to 3 years before clinical symptoms.

Cost effective diagnostic tool

“It is thought that these phospholipids, which are important constituents of cell membranes, reflect changes in the integrity of membranes which occur 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 either expensive (such as brain imaging) or invasive for the patient  (such as obtaining spinal fluid samples).

”The problem with current AD treatments is that they only help to alleviate symptoms, so a number of treatments aimed at stopping underlying mechanisms of AD are currently in development, including our own work at the Institute of Integrative Biology, in which we have developed chemically synthesized compounds based on natural sugars, called heparan sulphates, which are potent inhibitors of the enzyme beta-secretase.

“This enzyme is responsible for generating the small peoptides that accumulate in plaques in the brains of people affected with AD, and is a key target for treating an underlying cause of the disease. Successful development of such drugs could result in disease-modifying therapies which could slow or even halt disease progression.

“However, the development of AD proceeds silently for up to a decade or more before any symptoms emerge, and some drug trials may well have failed due to being tested too late in the disease process to produce real benefit for the patients. So it is now clear that treatment early in the disease process will be critical for the most effective outcomes.

Testing pre-symptomatic treatment

“The blood phospholipid changes discovered by Federoff and his colleagues may provide a sensitive measure of early neurodegenerative events, and this could provide an initial approach for selecting groups of patients suitable for testing pre-symptomatic treatment with new disease-modifying drugs.

Further research is clearly needed to confirm the initial work of the group. The phospholipids they have revealed may provide clues for extending biomarker panels to further improve the accuracy of testing. They might also permit even earlier diagnosis of AD beyond the current 3 year lead time they describe.  Extending their study to a much larger group of patients is the key next step.

“If the data holds up this should lead to new opportunities for big advances in early treatment trials.”