New Blood Test Can Detect Unique Biomarker for Alzheimer’s Neurodegeneration

There is no cure for Alzheimer’s disease and few treatments. Although it has been shown that early detection can help delay its onset, there is a lack of definitive and affordable tests to do so, according to BrightFocus Foundation’s Alzheimer’s Disease Research grantee Thomas Karikari, PhD, an assistant professor of psychiatry at the University of Pittsburgh.

The holy grail has been a blood test for Alzheimer’s disease, a handful of which are now available in the United States. Dr. Karikari and colleagues developed an innovative new test to detect a less frequently measured biomarker of Alzheimer’s disease neurodegeneration in the blood: brain-derived tau, or BD-tau. The results of their study were published in the journal Brain.

BD-tau, which is specific to Alzheimer’s disease, outperforms existing blood tests used to detect Alzheimer’s-related neurodegeneration.

Diagnosing Alzheimer’s disease

Until recently, Alzheimer’s disease could only be diagnosed by a biopsy of the brain during an autopsy. And although modern technology has made it possible to diagnose the disease in people living with Alzheimer’s, it is not a simple diagnosis.

“At present, diagnosing Alzheimer’s disease requires neuroimaging. These 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,” Dr. Karikari said in a press release issued by the University of Pittsburgh on the study.

The prerequisites for an Alzheimer’s diagnosis are the presence of a confirmatory biomarker (amyloid and tau), through neuroimaging, cerebrospinal fluid (CSF), or more recently, blood, and neuropsychological testing that demonstrates cognitive impairment. Although current blood tests can detect abnormalities in plasma amyloid beta and a phosphorylated form of tau, their value is limited for a variety of reasons.

First, amyloid does not affect everyone in the same way. While the presence of amyloid is required for an Alzheimer’s diagnosis, many people have amyloid in their brains yet show no cognitive impairment.

The presence of amyloid and tau may also be due to other neurodegenerative conditions that cause dementia, such as Lewy body dementia, Creutzfeldt-Jakob disease, and cerebral amyloid angiopathy, to name a few.

Finally, because blood biomarkers are obtained from circulating blood, it is unknown whether these toxic proteins originated in the brain or from other peripheral organs. Detecting abnormal proteins in the blood is not enough for Alzheimer’s disease diagnosis.

To optimize existing blood-based biomarker testing, Dr. Karikari and his colleagues designed a special antibody that selectively binds to BD-tau and validated it in 600 patient samples (both deceased and living patients with early Alzheimer’s) from five independent cohorts. They found that the levels of BD-tau detected in their samples matched levels of tau in cerebrospinal fluid, which is the gold standard. In addition, brain autopsy analyses showed that the levels of BD-tau correlated with the severity of amyloid plaques and tau tangles in the brain tissue.

A path to greater inclusion

Dr. Karikari and his colleagues believe monitoring blood levels of BD-tau may lead to better clinical trial design and inclusion of patients from populations traditionally not enrolled in Alzheimer’s treatments.

“There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background,” he said. “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.”

These studies are crucial to ensuring that the biomarker results are applicable to people from all backgrounds and will pave the way to making BD-tau commercially available for widespread clinical and prognostic use, the University of Pittsburgh reports.

What’s next

Next, Dr. Karikari and his team will conduct large-scale clinical validation of BD-tau in blood across a range of research groups, including those that recruit participants from diverse racial and ethnic backgrounds, memory clinics, and the community. Older adults with no biological evidence of Alzheimer’s disease will be included as well as individuals at different stages of the disease. These studies will also lead to more information about how BD-tau changes throughout the course of the disease, providing a better way to assess an individual’s disease stage.

“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,” Dr. Karikari said.