Blood Test Accurately Detects Alzheimer’s

Researchers in Pennsylvania have developed a blood test to detect a novel marker of Alzheimer’s disease neurodegeneration. The biomarker, called brain-derived tau (BD-tau), outperforms current blood diagnostic tests used clinically to detect Alzheimer’s-related neurodegeneration and correlates well with results from invasive cerebrospinal fluid (CSF) tests.

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. The development of simple tools detecting signs of Alzheimer’s in the blood without compromising on quality is an important step toward improved accessibility. 

“At present, diagnosing Alzheimer’s disease requires neuroimaging,” says senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at University of Pittsburgh School of Medicine. “Those tests are expensive and take a long time 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.”

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. But 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 aren’t influenced by potentially misleading contaminants produced elsewhere in the body. For example, blood levels of neurofilament light, a protein marker of nerve cell damage, become elevated in Alzheimer’s disease, Parkinson’s, 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.

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. To achieve this, they designed a special antibody that selectively binds to BD-tau, making it easily detectible 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 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. Levels of BD-tau also correlated with the severity of amyloid plaques and tau tangles in the brain tissue confirmed via brain autopsy analyses.

Scientists hope that monitoring blood levels of BD-tau could improve clinical trial design and facilitate screening and enrollment of patients from populations that historically haven’t been included in research cohorts. “There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background,” says Karikari. “To develop better drugs, trials need to enroll people from varied backgrounds and not just those who live close to academic medical centers. A blood test is cheaper, safer, and easier to administer, and it can improve clinical confidence in diagnosing Alzheimer’s and selecting participants for clinical trial and disease monitoring.”

The findings were published recently in Brain, a peer-reviewed journal.