EU.- An international team of neuroscientists led by the University of Pittsburgh (Pitt), in the US, developed a test to detect a new marker of Alzheimer’s disease neurodegeneration in a blood sample. The biomarker, called brain-derived tau (BD-tau), outperforms current diagnostic tests in blood. It is disease-specific and correlates well with biomarkers of Alzheimer’s neurodegeneration in cerebrospinal fluid (CSF), they published Tuesday.

A complex and expensive diagnosis

Today, to diagnose Alzheimer’s, doctors use guidelines established a decade ago. These guidelines call for simultaneous detection of amyloid plaques, tau tangles (formed by multiple phosphorylation of intracellular microtubule-associated tau protein), and neurodegeneration in the brain (either by imaging or by analysis of CSF samples). Unfortunately, both approaches to detect neurodegeneration in the brain have practical and economic limitations.

In particular, obtaining neuroimaging is complicated. “These tests are expensive and time consuming to schedule, and many patients, even in the US, don’t have access to scanners,” explained lead author Thomas Karikari, a professor of psychiatry at Pitt. Therefore, it is necessary to develop convenient and reliable disease biomarkers in blood samples, the collection of which is minimally invasive and requires fewer resources.

The scientists explained that blood levels of light neurofilaments, a protein that markers nerve cell damage, rise with Alzheimer’s, Parkinson’s and other dementias, making it ineffective in differentiating Alzheimer’s from other neurodegenerative conditions. The biggest problem lies in the detection of brain-specific neurodegeneration markers in the blood (BD-tau), which are not produced in other parts of the body.

The solution

Karikari and his team developed a technique to detect BD-tau. To do this, they designed a special antibody that selectively binds to BD-tau, making it easily detectable in blood. They validated their assay in more than 600 patient samples.

The tests showed that the BD-tau levels detected in samples from Alzheimer’s patients using the new assay matched CSF tau levels and reliably distinguished Alzheimer’s disease from other neurodegenerative diseases. BD-tau levels also correlated with the severity of amyloid plaques and tau tangles in brain tissue confirmed by brain autopsy analyses.

The scientists hope that monitoring BD-tau blood levels could improve clinical trial design and facilitate detection and recruitment of patients from populations that have not historically been included in research cohorts. The results were published this Tuesday in Brain. “The most important utility of blood biomarkers is to improve people’s lives and improve clinical confidence and risk prediction in the diagnosis of Alzheimer’s disease,” Karikari said.

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