Blood test can detect Alzheimer's neurodegeneration biomarker in blood: Pitt Study

Currently, to diagnose Alzheimer's disease, clinicians use guidelines set in 2011 by the National Institute on Aging and the Alzheimer's Association. 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 by analyzing CSF samples.

Unfortunately, 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.

A group of neuroscientists led by a University of Pittsburgh School of Medicine researcher developed a test to detect a novel marker of Alzheimer's disease neurodegeneration in a blood sample. A study on their results was published in Brain.

The biomarker, called "brain-derived tau," or BD-tau, 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).

"At present, diagnosing Alzheimer's disease requires neuroimaging," said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. "Those tests are expensive and take a longtime to schedule, and a lot of patients, even in the U.S., don't have access to MRI and PET scanners. Accessibility is a major issue."

The development of simple tools 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," Karikari said.

Current blood diagnostic methods canaccurately detect abnormalities in plasma amyloid beta and the phosphorylatedform of tau, hitting two of the three necessary checkmarks to confidentlydiagnose Alzheimer's. But the biggest hurdle in applying the AT(N) Framework toblood samples lies in the difficulty of detecting markers of neurodegenerationthat are specific to the brain and aren't influenced by potentially misleadingcontaminants produced elsewhere in the body.

For example, blood levels of neurofilamentlight, a protein marker of nerve cell damage, become elevated in Alzheimer'sdisease, Parkinson's and other dementias, rendering it less useful when tryingto differentiate Alzheimer's disease from other neurodegenerative conditions.On the other hand, detecting total tau in the blood proved to be lessinformative than monitoring its levels in CSF.

By applying their knowledge of molecularbiology and biochemistry of tau proteins in different tissues, such as thebrain, Karikari and his team, including scientists at the University ofGothenburg, Sweden, developed a technique to selectively detect BD-tau whileavoiding free-floating "big tau" proteins produced by cells outside the brain.

To do that, they designed a special antibodythat selectively binds to BD-tau, making it easily detectible in the blood.They validated their assay across over 600 patient samples from fiveindependent cohorts, including those from patients whose Alzheimer's diseasediagnosis was confirmed after their deaths, as well as from patients withmemory deficiencies indicative of early-stage Alzheimer's.

The tests showed that levels of BD-taudetected in blood samples of Alzheimer's disease patients using the new assaymatched with levels of tau in the CSF and reliably distinguished Alzheimer'sfrom other neurodegenerative diseases. Levels of BD-tau also correlated withthe severity of amyloid plaques and tau tangles in the brain tissue confirmedvia brain autopsy analyses.

Scientists hope that monitoring blood levelsof BD-tau could improve clinical trial design and facilitate screening andenrollment of patients from populations that historically haven't been includedin research cohorts.

"There is a huge need for diversity inclinical research, not just by skin color but also by socioeconomicbackground," said Karikari. "To develop better drugs, trials need to enrollpeople from varied backgrounds and not just those who live close to academicmedical centers. A blood test is cheaper, safer and easier to administer, andit can improve clinical confidence in diagnosing Alzheimer's and selectingparticipants for clinical trial and disease monitoring."

Reference:

Thomas Karikari et al,Brain-derived tau: anovel blood-based biomarker for Alzheimer's disease-typeneurodegeneration,Brain,DOI: 10.1093/brain/awac407