The biomarker, known as “brain-derived tau,” or BD-tau, performs better clinically than current blood diagnostic tests for Alzheimer’s-related neurodegeneration.
It is specific to Alzheimer’s disease and has a good correlation with biomarkers of Neurodegeneration in Blood found in the cerebrospinal fluid (CSF).
According to senior author and assistant professor of psychiatry at Pitt Thomas Karikari, Ph.D., “At present, diagnosing Alzheimer’s disease requires neuroimaging.” Many patients, even in the United States, lack access to MRI and PET scanners, which are costly and time-consuming to schedule. A major issue is an accessibility.
Clinicians currently use guidelines established in 2011 by the Alzheimer’s Association and the National Institute on Aging to diagnose Alzheimer’s disease.
Unfortunately, both approaches have practical and financial limitations, necessitating the creation of convenient and dependable AT(N) biomarkers in blood samples that are easy to collect and require fewer resources. According to Karikari, an important step toward making Alzheimer’s disease more accessible is the creation of low-cost, high-quality tools that can detect Alzheimer’s disease symptoms in the blood.
According to Karikari, “the most important utility of blood biomarkers is to improve clinical confidence and risk prediction in Alzheimer’s disease diagnosis” and “to make people’s lives better.”
When attempting to distinguish Alzheimer’s disease from other neurodegenerative conditions, blood levels of neurofilament light, a protein marker of nerve cell damage, become elevated in Alzheimer’s, Parkinson’s, and other dementias. However, compared to monitoring its concentrations in CSF, total tau detection in the blood proved to be less informative.
Karikari and his team, which included researchers from the University of Gothenburg in Sweden, developed a method to selectively detect BD-tau while avoiding free-floating “big tau” proteins produced by cells outside the brain by applying their knowledge of the molecular biology and biochemistry of tau proteins in various tissues, such as the brain.
In order to accomplish this, they developed a specific antibody that selectively binds to BD-tau and makes it simple to locate in blood.
According to the tests, the levels of BD-tau found in the CSF and blood samples of Alzheimer’s disease patients consistently distinguished Alzheimer’s disease from other neurodegenerative diseases. Brain autopsy analyses confirmed that levels of BD-tau also correlated with the severity of amyloid plaques and tau tangles in the brain tissue.
Monitoring BD-tau levels in the blood may, according to scientists, facilitate screening and enrollment of patients from historically excluded populations for research cohorts and enhance the design of clinical trials.
Karikari stated, “There is a huge need for diversity in clinical research, not just in terms of skin color but also in terms of socioeconomic background.” Trials must include participants from a variety of backgrounds, not just those who live close to academic medical centers, in order to develop better drugs. A blood test can improve clinical confidence in diagnosing Alzheimer’s and selecting participants for clinical trials and disease monitoring because it is less expensive, safer, and easier to administer.
Karikari and his team intend to carry out large-scale clinical validation of blood BD-tau in a variety of research groups, including those that recruit participants from a variety of racial and ethnic backgrounds, memory clinics, and the general public. In addition, participants in these studies will include older adults at various stages of the disease as well as those without any biological evidence of the condition. These projects will pave the way for the commercial availability of BD-tau for widespread clinical and prognostic use.
An example: Tau from the brain: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration” by Fernando Gonzalez-Ortiz, Michael Turton, Przemyslaw R Kac, Denis Smirnov, Enrico Premi, Roberta Ghidoni, Luisa Benussi, Valentina Cantoni, and Claudia Saraceno; Fernando Gonzalez-Ortiz, B.S., Przemyslaw Kac, B.S., Nicholas Ashton, Ph. Peter Harrison, Ph.D., and Michael Turton, Ph.D., both of Bioventix Plc, Farnham, United Kingdom; Douglas Galasko, MD, and Denis Smirnov, B.S., both of the University of California, San Diego; Barbara Borroni, M.D., Enrico Premi, M.D., Valentina Cantoni, Ph.D., Jasmine Rivolta, Ph.D., and the University of Brescia, Italy; and Claudia Saraceno, Ph.D., of the RCCS Istituto Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, as well as Roberta Ghidoni, Ph.D., Luisa Benussi, and Claudia Saraceno.
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