Scientists in Japan and Australia have developed a blood test that can identify people who have high levels of a protein associated with Alzheimer's disease. If confirmed by further research, this long-sought test could help in the increasingly desperate search for therapies that halt the progression of dementia, which affects tens of millions of people worldwide.
The test identifies people whose brains have high levels of amyloid-β, a protein that is a key player in Alzheimer’s disease, and which may either cause dementia or be a symptom of it. The researchers hope that drug developers could use the test to recruit individuals with dementia into clinical trials before irreversible damage to their brains has occurred — thus making the trials more reliable.
Molecular biologist Katsuhiko Yanagisawa at the Center for Development of Advanced Medicine for Dementia in Obu, Japan, and his colleagues developed the prototype biomarker test. They published their work online on 31 January in Nature1.
Scientists around the world have been searching for a simple blood test for dementia for the past 15 years. “At first it wasn’t obvious that it would be possible for brain pathology to be measurable in the blood, but we have been getting ever closer,” says neuroscientist Simon Lovestone at the University of Oxford, UK, who has led other studies to find blood biomarkers for Alzheimer’s disease. “This paper provides the best results I’ve seen so far.”
High failure rate
All candidate drugs designed to halt Alzheimer’s disease have failed in clinical trials so far, and many pharmaceutical companies have abandoned the field. Scientists suspect that the design of such trials might be the problem, rather than the drugs being tested. Until now, there has been no reliable way to identify people with the early stages of dementia, so most clinical trials have recruited people whose clinical symptoms are already apparent. At this point, brain damage associated with amyloid-β has already occurred and it may be too late to reverse it, says Yanagisawa.
Until now, the only way to identify amyloid-β in the brain — short of an autopsy — has been to image the brain using positron-emission tomography, or to measure levels of the protein directly in cerebrospinal fluid from the spinal cord. Both of these procedures have been used to help recruit patients into recent trials, but the tests are expensive and uncomfortable.
To measure the levels of several amyloid-β fragments in blood samples, as well as a fragment of a larger protein from which amyloid-β derives, Yanagisawa and his colleagues combined two existing techniques — immunoprecipitation and mass spectroscopy. Their results matched those achieved through brain imaging and the analysis of spinal-cord fluid in two separate cohorts involving 121 people in Japan and 252 people in Australia. Each cohort included individuals aged between 60 and 90. Some of the participants were healthy; some showed mild impairment in their cognitive skills; and some had Alzheimer’s disease.
The authors say that larger and more long-term studies are needed to confirm how accurate the blood test is at identifying high levels of amyloid-β in human brains. If it is highly accurate, then the test could help recruitment for clinical trials, because it is relatively easy and cheap to do.