A biomarker in the blood detects early signs of Alzheimer's

A biomarker in the blood detects early signs of Alzheimer’s

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A team of neuroscientists from the American University of Pittsburgh, together with experts from European countries, has developed an advanced test that, based on a biomarker, detects signs of neurodegeneration in blood in Alzheimer’s disease.

These US neuroscientists chose Brain to disseminate a study presenting the development and validation of an ultrasensitive immunoassay and clinical performance results in five independent cohorts, for an improved blood-based biomarker of t-tau, which they call BD-tau.

In a nutshell, have shown that plasma BD-tau is a biomarker of Alzheimer’s-type neurodegeneration“which can discriminate between this poorly verified by autopsy, from other neurodegenerative diseases and, moreover, is associated with the clinical severity of the disease in the neuropathology cohort”.

“The importance of this biomarker, which also explains these findings, -they add- is that blood and CSF (cerebrospinal fluid) levels correlate strongly in paired samples. The assay was developed using a monoclonal antibody that selectively binds to CNS tau isoforms (hence the name BD-tau).”

In addition, BD-tau in blood, like NfL (Neurofilament light chain), has high diagnostic accuracy in detecting neurodegeneration in Alzheimer’s disease. However, NfL plasma did not.

Alzheimer’s blood biomarker

Professor Thomas Karikari, lead author of this paper, recalls that Alzheimer’s diagnosis currently requires neuroimaging, “expensive tests that take a long time to program, and many patients, even in the US, do not have access to MRI and PET scanners. Accessibility is a major issue.”

In the diagnosis of this dementia, the guidelines established in 2011 by the National Institute on Aging and the Alzheimer’s Association are used. The guidelines, called the AT(N) Framework, call for detection of three distinct components of disease pathology: presence of amyloid plaques, tau tangles, and neurodegeneration in the braineither by imaging or by analyzing cerebrospinal fluid samples.

This neuroscientist recognizes that these approaches have economic and practical limitations, which is why it is necessary to develop effective AT(N) biomarkers in blood samples, the collection of which is minimally invasive and requires fewer resources.

Developing simple tools that detect signs of Alzheimer’s in blood without compromising quality is an important step toward better accessibility, according to Karikari. “The most important utility of a blood biomarker -he stresses- is to improve people’s lives and improve clinical confidence and risk prediction in the diagnosis of Alzheimer’s disease”.

Current blood diagnostic methods can accurately detect abnormalities in plasma amyloid beta and the phosphorylated form of tau, hitting two of the three checkmarks needed to confidently diagnose Alzheimer’s disease.

Differentiating Alzheimer’s from other neurodegenerative diseases

But the biggest hurdle in applying the AT(N) Framework to blood samples lies in the difficulty of detecting markers of neurodegenerationwhich are specific to the brain and not influenced by potentially misleading contaminants produced elsewhere in the body.

For example, blood levels of light neurofilaments, a protein that markers nerve cell damage, are elevated in Alzheimer’s, Parkinson’s, and other dementias, making it less useful when trying to differentiate Alzheimer’s from other neurodegenerative conditions.

By applying their knowledge of the molecular biology and biochemistry of tau proteins in different tissues, such as the brain, Professor Karikari and his team, together with Swedish neuroscientists from the University of Gothenburg, developed a technique to selectively detect BD-tau.

For it, designed a special antibody that selectively binds to BD-tau, making it easily detectable in blood. They validated their assay in more than 600 patient samples from five independent cohorts, including those from patients whose diagnosis of Alzheimer’s disease was confirmed after their death, as well as from patients with early-stage memory deficits typical of Alzheimer’s.

The tests showed that the levels of BD-tau detected in blood samples from Alzheimer’s disease patients using the new assay matched the levels of tau in cerebrospinal fluid.

Thus they were able to confidently differentiate Alzheimer’s disease from other neurodegenerative diseases. BD-tau levels also correlated with the severity of amyloid plaques and tau tangles in brain tissue.confirmed by brain autopsy analysis.

accessible biomarker

“There is a great need for diversity in clinical research, not only because of skin color but also because of socioeconomic status,” said Professor Karikari. To develop better drugs, trials need to include people from diverse backgrounds, not just those who live near academic medical centers. A blood test is cheaper, safer and easier to administerand may improve clinical confidence in the diagnosis of Alzheimer’s disease and the selection of participants for the clinical trial and the follow-up of the disease”.

Professor Karikari and his team will conduct a large-scale clinical validation of BD-tau in blood across a wide range of research groups, including those recruiting volunteers from various racial, ethnic, and other backgrounds. These studies will include older adults without biological evidence of Alzheimer’s disease, as well as those at different stages of the disease.

In addition to those already mentioned, neuroscientists from Bioventix Plc and from the Universities of California in San Diego and Brescia, in Italy, as well as the Centro San Giovanni di Dio Fatebenefratelli participated in the study.

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