A group of neuroscientists developed a test to detect a novel marker of Alzheimer’s disease neurodegeneration in a blood sample. A study on their results, which was led by a University of Pittsburgh School of Medicine researcher, was published on December 27 in the journal 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 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.”
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, 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 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.
By applying their knowledge of molecular biology and biochemistry of tau proteins in different tissues, such as the brain, 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 do that, 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,” said 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.”
Karikari and his team are planning to conduct large-scale clinical validation of blood BD-tau in a wide range of research groups, including those that recruit participants from diverse racial and ethnic backgrounds, from memory clinics, and from the community. Additionally, these studies will include older adults with no biological evidence of Alzheimer’s disease as well as those at different stages of the disease. These projects are crucial to ensure that the biomarker results are generalizable to people from all backgrounds, and will pave the way to making BD-tau commercially available for widespread clinical and prognostic use.
Reference: “Brain-derived tau: 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, Claudia Saraceno and Jasmine Rivolta, 27 December 2022, Brain.
Additional authors of this study are Fernando Gonzalez-Ortiz, B.S., Przemyslaw Kac, B.S., Nicholas Ashton, Ph.D., and Henrik Zetterberg, M.D., Ph.D., of the University of Gothenburg, Sweden; Michael Turton, Ph.D., and Peter Harrison, Ph.D., of Bioventix Plc, Farnham, U.K.; Denis Smirnov, B.S., and Douglas Galasko, M.D., of the University of California, San Diego; Enrico Premi, M.D., Valentina Cantoni, Ph.D., Jasmine Rivolta, Ph.D., and Barbara Borroni, M.D., of the University of Brescia, Italy; and Roberta Ghidoni, Ph.D., Luisa Benussi, Ph.D., and Claudia Saraceno, Ph.D., of RCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
This research was supported by the Swedish Research Council (Vetenskåpradet; #2021-03244), the Alzheimer’s Association (#AARF-21-850325), the BrightFocus Foundation (#A2020812F), the International Society for Neurochemistry’s Career Development Grant, the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Swedish Parkinson Foundation (Parkinsonfonden), Gamla Tjänarinnor Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Agneta Prytz-Folkes & Gösta Folkes Foundation (#2020-00124), the Gun and Bertil Stohnes Foundation and the Anna Lisa and Brother Björnsson’s Foundation, among other sources.
Testing for BD-tau is inherently inferior to preventing it from forming in the first place. What these allergy ignorant and incompetent researchers are still unaware of is that Dr. Arthur F. Coca identified, studied and reported on a kind (increases pulse rate; my kind) of chronic subclinical non-IgE-mediated food (minimally) allergy reaction by 1935 which mainstream medicine still fails to recognize and research. Long since, just to recover my own former better state of health, I’ve personally related his basic allergy findings to a high serum level of uric acid (asymptomatic gout), sluggish metabolism (low oral temperature), high blood pressure, cholesterol and triglycerides, obesity, lower blood oxygen (e.g., very affordable finger pulse-oximeter), acidic saliva/urine pH and serious calcium and phosphorus deficiencies, all aggravated since 1980 with FDA approved added ‘cultured-free’ (can cross the blood/brain barrier) MSG (as an alleged “flavor enhancer”). As the successful “cytotoxic blood testing for food allergies” I had in late 1981 is no longer available, why not spend the research money on developing a new (and/or resurrecting the old) affordable, convenient and reliable lab testing method for my kind of allergies, instead of just allowing millions of more victims and their families to suffer, for greater profits?
Unsure at what point inclusion of a more “diverse” pool of subjects starts to skew valid data for typical subjects per a given population. And more importantly is research being held up by unavailability of enough “diverse” subjects for a given project? I’d say stick with what is most beneficial for the most people in a population and expand from there.
Diversity just means kick whites out of their countries.
Thank you, Doctor Karikari, and team. Better tests means earlier diagnosis and potentially treatment. Though, as far as I know, regular cardiovascular exercise and maybe sauna that similarly elevates heart rate, and maybe hyperbaric oxygen therapy can slow the disease. But maybe I am not up on everything. Hopefully more will be on the way, and tests like this will aid studies that might find treatments.
Charles Shaver is a better neurologisy than all authors of this bull dookie.
Our Associates indeed PREVENT dementia, we REVERSE Alzheimers affects.
We , UNlike Auschwitz Murderers Assassins AMA we DO Comprehend.
Prevention is bliss, repairing rhe neural net without any. pHarma pHaroah nor ama ginsu. ..you will not believe.
You do not now, see.
Well maybe you moron ama will learn one day.
Soon please, you are embarrassing to true neuro-cannabinoid science