A group of neuroscientists, led by the University of Pittsburgh, US, have identified the biomarker, called "brain-derived tau", or BD-tau, which outperforms current blood diagnostic tests used to detect Alzheimer's-related neurodegeneration clinically.
It is specific to Alzheimer's disease and correlates well with Alzheimer's neurodegeneration biomarkers in the cerebrospinal fluid (CSF), the study said.
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A study on their results was published in the journal Brain. "At present, diagnosing Alzheimer's disease requires neuroimaging," said senior author Thomas Karikari, University of Pittsburgh. "Those tests are expensive and take a long time to schedule, and a lot of patients, even in the US, do not have access to MRI and PET scanners. Accessibility is a major issue," he added.
Currently, to diagnose Alzheimer's disease, clinicians use guidelines set in 2011 by the National Institute on Aging and the Alzheimer's Association, US. The guidelines, called the AT(N) Framework, require detection of three distinct components of Alzheimer's pathology—the presence of amyloid plaques, tau tangles and neurodegeneration in the brain—either by imaging or analysing CSF samples.
"Both approaches suffer from economical and practical limitations, dictating the need for development of convenient and reliable AT(N) biomarkers in blood samples, collection of which is minimally invasive and requires fewer resources," said Karikari.
"The development of simple tools for detecting signs of Alzheimer's in the blood without compromising on quality is an important step toward improved accessibility," said Karikari. "The most important utility of blood biomarkers is to make people's lives better and to improve clinical confidence and risk prediction in Alzheimer's disease diagnosis," he added.
Current blood diagnostic methods can accurately detect abnormalities in plasma amyloid beta and the phosphorylated form of tau, hitting two of the three necessary checkmarks to confidently diagnose Alzheimer's.
However, the biggest hurdle in applying the AT(N) Framework to blood samples lies in the difficulty of detecting markers of neurodegeneration that are specific to the brain and are not influenced by potentially misleading contaminants produced elsewhere in the body, the study said.
For example, blood levels of neurofilament light, a protein marker of nerve cell damage, become elevated in Alzheimer's disease, Parkinson's disease and other dementias, rendering it less useful when trying to differentiate Alzheimer's disease from other neurodegenerative conditions.
On the other hand, detecting total tau in the blood proved to be less informative than monitoring its levels in CSF. By applying their knowledge of molecular biology and biochemistry of tau proteins in different tissues, such as the brain, Karikari and his team, including scientists at the University of Gothenburg, Sweden, developed a technique to selectively detect BD-tau while avoiding free-floating "big tau" proteins produced by cells outside the brain, the study said.
To do that, they designed a special antibody that selectively binds to BD-tau, making it easily detectable in the blood. They validated their assay across over 600 patient samples from five independent cohorts, including those from patients whose Alzheimer's disease diagnosis was confirmed after their deaths, as well as from patients with memory deficiencies indicative of early-stage Alzheimer's, the study said.
The tests showed that levels of BD-tau detected in blood samples of Alzheimer's disease patients using the new assay matched with levels of tau in the CSF and reliably distinguished Alzheimer's from other neurodegenerative diseases, the study said.
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Levels of BD-tau also correlated with the severity of amyloid plaques and tau tangles in the brain tissue confirmed through brain autopsy analyses, the study said. Scientists hope that monitoring blood levels of BD-tau could improve clinical trial design and facilitate the screening and enrollment of patients from populations that historically have not been included in research cohorts.
