A reliable, simple test detects early-stage Alzheimer’s
Current ways of diagnosing Alzheimer’s disease are costly, cumbersome, invasive and time-consuming. A blood test is a substantial improvement, allowing people to make lifestyle changes earlier on in the disease, to try and mitigate its effects. Knowing if they have the condition can also help people to decide on their priorities and to plan. One novel blood test developed by the EU-supported VERDAD project could offer clinicians valuable insights. Emerging immunotherapies to treat Alzheimer’s are coming onto the market, but some will provoke side effects: “We expect that our blood-based assay will also help clinicians recognise which patients will be at risk of developing such side effects,” says Håkon Sæterøy, the CEO of www.pre-diagnostics.com (Pre Diagnostics), the company behind the EU’s VERDAD project.
A new way of assessing beta-amyloid
VERDAD’s blood test reveals disease-specific information on the key hallmarks of innate immune beta-amyloid (Aβ) metabolism. “Our novel blood test monitors the immune intracellular clearance of Aβ, a neurotoxic metabolite believed to be an early driver of the neurodegenerative cascade caused by Alzheimer’s disease,” explains Sæterøy. Monitoring the innate immune Aβ metabolism shines a light on the way the disease develops over time and gives clinicians a way of assessing the impact of medication on the progression of the condition. “Amyloid-β metabolism is modified years before clinical symptoms appear in patients. Our convenient, blood-based biomarker quantifies this main, ongoing neurodegenerative biochemical process.” The fact that Aβ turnover is measured intracellularly in monocytes from blood means interference from surrounding blood cells and the peripheral environment can be avoided. “This addresses some of the inherent limitations associated with current blood-based approaches employed for Alzheimer’s disease biomarker discovery,” notes Sæterøy. This new and unique use of monocytes as sample material, allows intracellular measurements of biomarkers in the tiny sample volume. In combination with the ultra-sensitive digital immunoassay, this enables much earlier disease detection.
Advances in analysis
While the blood sample can be taken in the normal way, the analysis would be done at a central lab. Target cells are purified by a positive isolation method using antibodies selective for monocytes bound to paramagnetic beads. By placing the sample on a magnet, bead-bound monocytes are separated from the rest of the sample. Before analysis, the cell membranes are broken down making the cell content available for analysis. “Our new method of monocyte extraction means samples are sent to our service laboratory, or to a partnering laboratory, for example in the United States. We are aiming at covering the Nordic market ourselves, while we are looking for such laboratory partners that would be interested in building this business in Europe and in the United States,” Sæterøy adds. The project has been collaborating with Akershus University Hospital (Ahus) and other Norwegian hospitals, which have provided blood samples for our clinical study. “Our assays are now applied by Ahus and their clinical partners in ongoing and planned clinical studies on Alzheimer’s disease, as research-only tools.” The team now intends to collect further clinical evidence for the test over the next 12 months, using more blood samples from their collaborators, and to share these results with potential licence partners and customers. “We worked hard for 6 years to achieve this breakthrough. The first time we were able to detect these small beta-amyloid peptides in monocytes was thrilling, of course. Now a new phase of the work can begin: the optimisation of the assays followed by clinical validation and CE marking.”
Keywords
VERDAD, Alzheimer’s disease, beta-amyloid, blood test, Pre Diagnostics, amyloid-β metabolism, blood-based biomarker
