Researchers Develop A Novel Biomarker Test That Can Detect Alzheimer’s Disease Neurodegeneration In Blood Samples

Approximately 6.5 million U.S. adults are currently living with Alzheimer’s disease (AD)– a neurodegenerative disease that impacts memory, thought processes, and behavior. But even though there is currently no cure for AD, it is still optimal for patients to receive an early diagnosis.
Early diagnoses provide patients with a plethora of benefits. Primarily, they have a higher chance of benefiting from available therapies and interventions.
These patients may also have the opportunity to participate in clinical trials since early diagnoses will earn them greater candidacy in a wider variety of research studies.
And recently, new research conducted by the University of Pittsburgh School of Medicine has made a groundbreaking discovery in this realm.
The study, led by Thomas Karikari, developed a test that can detect a novel biomarker of AD neurodegeneration from a patient’s blood sample.
The marker, known as brain-derived tau (BD-tau), actually outperformed the blood diagnostic tests currently used to detect AD-related neurodegeneration. Moreover, the test is specific to AD and works well with AD neurodegeneration biomarkers present in cerebrospinal fluid (CSF).
Perhaps the most notable benefit of this new test, though, is its potential for widespread accessibility.
“At present, diagnosing Alzheimer’s disease requires neuroimaging. 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,” explained Karikari.
Right now, clinicians are also using guidelines issued by the National Institute on Aging and the Alzheimer’s Association in 2011.

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These guidelines, known as the AT(N) framework, require three distinct components to be detected either via imaging or the analysis of CSF samples. These components include tau tangles, amyloid plaque presence, and brain neurodegeneration.
Unfortunately, though, both of these detection options pose severe economic limitations– signaling a desperate need for cost-effective and convenient AT(N) biomarker development in blood samples. This is also a minimally invasive procedure that requires much fewer resources.
The blood diagnostic methods currently used are able two check two of the three necessary benchmarks for diagnosing AD– the detection of abnormalities in the phosphorylated tau form and plasma amyloid beta.
The most significant challenge, though, is detecting biomarkers of neurodegeneration that are directly linked to the brain and are not influenced by any other contaminants produced in other parts of the body.
Yet remarkably, Karikari and his research team were able to develop a technique that selectively detects BD-tau while managing to avoid “big tau” proteins which are produced by cells located outside of the brain.
This was possible after the researchers designed a unique antibody that specifically binds to BD-tau, which ultimately makes it easier to detect in blood samples.
Then, this process was tested using over 600 patient samples obtained from five different cohorts.
These samples came from both patients whose AD diagnoses were confirmed post-mortem, as well as patients with memory impairment suggestive of early-stage AD.
The tests revealed that BD-tau levels detected in blood samples of AD patients matched the same detection levels in the cerebral spinal fluid. It also was able to reliably distinguish AD from other neurodegenerative diseases.
Finally, the detection of BD-tau levels correlated with tau tangles in the brain tissue and amyloid plaque severity– a finding which was confirmed using brain autopsy analyses.
So now, the researchers are hopeful that through the monitoring of BD-tau blood levels, clinical trial design could be improved, and screening may be facilitated. Additionally, patients from populations that have not historically been included in research cohorts may be allowed greater enrollment.
“There is a huge need for diversity in clinical research, not just by skin color but also by socioeconomic background,” Karikari 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.”
The researchers’ next steps include the launch of a large-scale effort to clinically validate blood BD-tau among a wide range of research groups, which recruit participants from memory clinics, the community, and diverse ethnic and racial backgrounds. The studies will also include older adults with no biological evidence of AD, in addition to patients at different stages of AD.
These steps are critical for ensuring that the biomarker results are applicable to patients from all backgrounds. Moreover, they are vital for making BD-tau a commercially available option for clinical use.
To read the study’s complete findings, which have since been published in Oxford Academic, visit the link here.
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