A newly developed blood test for Alzheimer’s disease not only aids in the diagnosis of the neurodegenerative condition but also indicates how far it has progressed, according to a study by researchers at Washington University School of Medicine in St. Louis and Lund University in Sweden.
Several blood tests for Alzheimer’s disease are already clinically available, including two based on technology licensed from WashU. Such tests help doctors diagnose the disease in people with cognitive symptoms, but do not indicate the clinical stage of the disease symptoms — that is, the degree of impairment in thinking or memory due to Alzheimer’s dementia. Current Alzheimer’s therapies are most effective in early stages of the disease, so having a relatively easy and reliable way to gauge how far the disease has progressed could help doctors determine which patients are likely to benefit from drug treatment and to what extent. The new test can also provide insight on whether a person’s symptoms are likely due to Alzheimer’s versus some other cause.
The study is published March 31 in Nature Medicine.
In the study, the researchers found that levels of a protein called MTBR-tau243 in the blood accurately reflect the amount of toxic accumulation of tau aggregates in the brain and correlate with the severity of Alzheimer’s disease. Analyzing blood levels of MTBR-tau243 from a group of people with cognitive decline, the researchers were able to distinguish between people with early- or later-stage Alzheimer’s disease and separate both groups of Alzheimer’s patients from people whose symptoms were caused by something other than Alzheimer’s disease.
“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” said co-senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at WashU Medicine. “In clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients.”
Tracking Alzheimer’s disease progression from blood
Alzheimer’s disease involves a build-up of a protein, called amyloid, into plaques in the brain, followed by the development of tangles of tau protein years later. Cognitive symptoms emerge around the time tau tangles become detectable, and symptoms worsen as the tangles spread. The gold standard for staging Alzheimer’s disease is positron emission tomography (PET) brain scans for amyloid plaques and tau tangles. Amyloid scans yield information about the presymptomatic and early symptomatic stages, while tau scans are useful for tracking later stages of the disease. PET brain scans are highly accurate but expensive, time-consuming and frequently unavailable outside of major research centers, so they are not widely used.
Bateman leads a team that is developing blood tests for Alzheimer’s disease as a more accessible alternative to brain scans. They have developed two blood tests that correlate closely with the amount of amyloid plaques in the brain. Both are now used by doctors to aid diagnosis. But until now, there has been no blood test that reports on tau levels in the brain.
In a previous study, Bateman and colleagues — including co-first authors Kanta Horie, PhD, a research associate professor of neurology at WashU Medicine, and Gemma Salvadó, PhD, then a postdoctoral researcher at Lund University, and co-senior author Oskar Hansson, MD, PhD, a professor of neurology at Lund University — showed that cerebrospinal fluid levels of MTBR-tau243 correlate closely with tau tangles in the brain. In the current study, the team extended the analysis to blood. A blood sample is easier to collect than cerebrospinal fluid, which is obtained via spinal tap.
The researchers developed a technique to measure MTBR-tau243 levels in people’s blood and compared it to the amount of tau tangles in their brains as measured by brain scans. They piloted the approach on data from two cohorts: volunteers at WashU Medicine’s Charles F. and Joanne Knight Alzheimer Disease Research Center, which included 108 people, and a subset of 55 people from the Swedish BioFINDER-2 cohort. To assess whether the approach was generalizable, they validated it in an independent dataset consisting of the remaining 739 people in the BioFINDER-2 cohort.