Brain: A new biomarker may help detect Alzheimer's disease neurodegeneration in the blood

Recently, a research report entitled "Brain-derived tau: a novel blood-based biomarker for Alzheimer's disease-type neurodegeneration" published in the international journal Brain, scientists from the University of Gothenburg and other institutions have developed a new detection technology through research.
It may be able to detect novel markers of neurodegenerative disease in Alzheimer's disease in blood samples from patients
.
This biomarker called brain-derived tau protein (BD-tau) has certain specificity for Alzheimer's disease due to the current blood diagnostic technology used clinically to detect Alzheimer's disease-related neurodegeneration, and it is also well correlated
with the neurodegenerative biomarker of Alzheimer's disease in cerebrospinal fluid.

Researcher Thomas Karikari said that the current diagnosis of Alzheimer's disease requires neuroimaging, and these tests are very expensive, often take a long time, and even in the United States, many patients do not have access to MRI and PET scans, and the availability of these imaging techniques is a major concern
.
Therefore, to diagnose Alzheimer's disease, clinical researchers used guidelines
developed by the National Institute on Aging and the Alzheimer's Association in 2011.
The guidelines, called the AT(N) framework, call for imaging or analyzing cerebrospinal fluid samples from the patient's body to detect three different components of Alzheimer's disease pathology, namely the presence of amyloid plaques in the brain, the presence of tau tangles, and the presence of
neurodegenerative lesions.

Unfortunately, these methods have certain economic and practical limitations, which urge scientists to develop convenient and reliable AT(N) biomarker tests for blood samples, which can collect blood samples in the least invasive way and require relatively little
information.
The researchers note that developing simple tools to detect signs of Alzheimer's disease in the blood without compromising quality could be an important step
toward improving access to technology.
Karikari, the researcher, said the most important use of blood biomarkers is to make people better and improve clinical confidence and risk prediction
in Alzheimer's disease diagnosis.

Current blood diagnostic methods can accurately detect abnormalities in plasma β amyloid and forest-borne forms of tau, allowing for two of the three necessary checkpoints to confidently diagnose Alzheimer's disease, but the biggest obstacle to applying the AT(N) framework to blood samples is that scientists have difficulty detecting neurodegenerative markers that are very specific to the brain, while not being affected
by potentially misleading contaminants produced elsewhere in the body 。 For example, levels of neurogenic cellulose, a protein marker of nerve cell damage, are elevated in Alzheimer's, Parkinson's and other dementias, making it less useful when trying to distinguish Alzheimer's disease from other neurodegenerative diseases; On the other hand, measuring the level of total tau protein in the blood is not as valuable as monitoring its level in the cerebrospinal fluid
.

New biomarkers may help detect Alzheimer's disease neurodegenerative disease
in the blood.

Image source: Brain (2022).
DOI:10.
1093/brain/awac407

By applying molecular biology and biochemistry to tau proteins in different tissues, such as the brain, the researchers developed a special technique that selectively detects BD-tau while avoiding the free-floating "big tau" protein
produced by accidental cells in the brain.
To do this, the researchers designed a special antibody that selectively binds to BD-tau, making it easier to detect
in the blood.
They also then confirmed their trial in studies of more than 600 patients from five separate study cohorts, including those diagnosed with Alzheimer's disease after death and those with early-stage Alzheimer's disease with memory
deficits 。 The results showed that BD-tau levels in blood samples from Alzheimer's disease patients detected using the new assay matched tau levels in cerebrospinal fluid and reliably distinguished Alzheimer's disease from other neurodegenerative diseases, and that BD-tau levels were also associated with
the severity of amyloid plaques and tau tangles in brain tissue confirmed by brain anatomy analysis.
The researchers hope that measuring blood levels of BD-tau will help improve the design of clinical trials and facilitate certain screening and recruitment studies
in populations that have not historically been included in the study cohort.

Researcher Karikari said that there is still a huge demand for diversity in clinical research, not only according to the color color of the population, but also according to the socioeconomic background, etc.
, in order to develop better drugs, clinical trials need to recruit people from different backgrounds, not just people living near academic medical centers; Blood tests are very cheap, safe, and easy to administer, improve clinical confidence in diagnosing Alzheimer's disease, and are not studied in selected participants for clinical trials and disease surveillance
.

The next step is for large-scale clinical validation of BD-tau in blood in a broader research group, including participants recruited from different racial and ethnic backgrounds, memory clinics, and the community.
In addition, these studies will include older adults who do not have biological evidence of Alzheimer's disease and elderly populations at different stages of the disease, which is important to ensure that the biomarker results obtained are generalized to people of all backgrounds, and will pave the way
for the commercialization of BD-tau for widespread clinical and prognostic use.

Taken together, the results suggest that brain-derived tau protein may reveal the potential to complete AT(N) strategies in the blood, which may help to evaluate Alzheimer's-disease-dependent neurodegenerative processes
for clinical and research purposes.
(Biovalley Bioon.
com)

Original source:

Fernando Gonzalez-Ortiz,Michael Turton,Przemysław R Kac, et al.
 Brain-derived tau: a novel blood-based biomarker for Alzheimer's disease-type neurodegeneration, Brain (2022).
DOI: 10.
1093/brain/awac407