A new blood test distinguishes neurodegeneration in Alzheimer’s disease from other types of dementia

summary: Researchers have developed a new blood test for brain-derived Tau that can monitor and track the progression of Alzheimer’s disease while excluding other types of dementia.

Source: University of Gothenburg

A new blood test that can track and follow neurodegeneration in Alzheimer’s disease – excluding other types of dementia. This is an innovation that has now been presented by researchers at the University of Gothenburg with their colleagues in Italy and the USA.

In recent years, much effort has been made to develop blood biomarkers that can help diagnose and monitor Alzheimer’s disease (AD). Tau—one of the key proteins involved in Alzheimer’s pathology—has been the focus of intense biomarker research.

New blood-based tau markers for phospholipid Alzheimer’s disease that have emerged in the past two years have demonstrated that it is possible to obtain an effective and accessible test for screening patients with suspected Alzheimer’s disease.

However, measuring brain proteins in blood is very challenging even with current technologies. Scientists at the University of Gothenburg and their industry partners designed a novel antibody that specifically targets tau isoforms that originate from the brain, by taking advantage of architectural differences in tau protein structure found in brain versus peripheral sources.

Addresses an unmet need

This breakthrough allowed them to develop a new blood test that specifically and selectively measures unphosphorylated tau coming from the brain into the bloodstream. This innovation addresses an urgent unmet need; A blood test that tracks neurodegenerative changes specifically in Alzheimer’s disease but not in other dementias.

The new brain-derived tau (BD-tau) test showed robust and stable technical performance in blood. Clinically, there were strong correlations between BD-tau levels in blood and CSF, indicating that the assay was measuring brain tau. Thanks to a collaboration between Italy, the USA and Sweden, they measured BD-tau levels in blood samples from 609 patients.

In a cohort of individuals who received a necropsy-verified diagnosis, plasma BD-tau was shown to be a marker of neurodegeneration that distinguishes Alzheimer’s disease from non-Alzheimer’s dementia. Remarkably, plasma BD-tau, but not neurofilament light (NfL), associated with amyloid plaque and tau crosslink loads in the brains of these individuals, showing its specificity for Alzheimer’s disease.

High differentiation accuracy

To demonstrate the clinical utility of these findings, the researchers studied two separate groups of memory clinics where participants had been diagnosed with Alzheimer’s disease or other dementia or controls. Again, plasma BD-tau had a higher accuracy for distinguishing Alzheimer’s disease from other dementia diseases, and also outperformed plasma NfL.

This shows a researcher testing a blood sample
New blood-based tau markers for phospholipid Alzheimer’s disease that have emerged in the past two years have demonstrated that it is possible to obtain an effective and accessible test for screening patients with suspected Alzheimer’s disease. The image is in the public domain

The results show that plasma BD-tau is a novel blood-based biomarker that can distinguish between AD and other types of dementia, and unlike other blood-based biomarkers such as NfL, BD-tau uniquely reflects the extent of neurodegeneration in Alzheimer’s patients.

Ten years ago, the National Institutes of Aging and Alzheimer’s Society USA proposed a framework for identifying and staging Alzheimer’s disease progression using biological evidence.

This framework, referred to as the AT(N) model, focuses on biomarkers of amyloid (A), tau (T), and neurodegeneration (N), and has been documented using cerebrospinal fluid (CSF) and neuroimaging biomarkers. CSF AT(N) markers include amyloid-beta (Aβ42/40), phosphorylated-tau (p-tau), and total tau.

A quick and easy-to-access blood test

However, it has not been possible to fully implement the AT(N) system using blood biomarkers. This is due to the deficiency of the N-marker showing specificity for the pathophysiology of Alzheimer’s disease. Plasma BD-tau allows complete serum AT(N) plotting as a true pathology-specific neurodegeneration marker of Alzheimer’s type.

From a research perspective, BD-tau would be useful for understanding neurodegenerative processes in Alzheimer’s disease and how they differ from those in other types of dementia. From a clinical perspective, BD-tau could easily be implemented as a rapid and accessible blood test for the diagnosis and monitoring of disease progression in patients with Alzheimer’s disease.

About this search for Alzheimer’s disease news

author: Margareta Gustafson Cubist
Source: University of Gothenburg
Contact: Margareta Gustafsson of Kobis University, Gothenburg
picture: The image is in the public domain

Original search: open access.
Brain-derived tau: a new blood-based biomarker for neurodegeneration of the Alzheimer’s disease typeBy And Blennow et al. brain


Summary

Brain-derived tau: a new blood-based biomarker for neurodegeneration of the Alzheimer’s disease type

See also

This indicates a brain and a question mark

Blood-based biomarkers of amyloid beta and tau phosphorus show good diagnostic accuracy and agreements with neuroimaging biomarkers and corresponding cerebrospinal fluid (CSF) in amyloid/tau/neurodegeneration [A/T/(N)] Framework for Alzheimer’s disease.

However, neurofilament light for a blood-based marker of neurodegeneration is not specific for Alzheimer’s disease while total tau shows no association with CSF total-tau. Recent studies indicate that total blood tau arises primarily from peripheral, non-cerebral sources.

We sought to address this challenge by creating an anti-tau antibody that selectively binds brain-derived tau and avoids the peripherally expressed ‘big tau’ isoform.

We applied this antibody to develop a supersensitive blood-based assay for brain-derived tau, and validated it in five independent cohorts (n = 609) including the blood-to-autopsy, CSF vital signs classification cohort and the memory clinic cohort.

In the paired samples, serum tau and brain-derived CSF were significantly correlated (rho = 0.85, s <0.0001), while total serum and CSF tau was not (rho = 0.23, s = 0.3364). Blood-derived tau showed equivalent diagnostic performance as total CSF and brain-CSF-derived tau to separate biomarker-positive Alzheimer participants from biomarker-negative controls.

Furthermore, brain-derived plasma tau accurately distinguished histologically confirmed Alzheimer’s disease from other neurodegenerative diseases (area under the curve = 86.4%) while light filaments were not (area under the curve = 54.3%).

These presentations were independent of the presence of comorbidities. plasma brain-derived tau (rho = 0.52–0.67, s = 0.003), but not light filaments (rho = −0.14–0.17, s = 0.501), was related to global and regional neurofibrillary synapse counts.

These findings were further validated in two groups of memory clinics where brain-derived tau distinguished Alzheimer’s disease from a host of other neurodegenerative disorders, including frontotemporal lobe degeneration and atypical Parkinson’s disorders (area under the curve up to 99.6%).

Notably, brain-derived plasma/serum tau binds to neurofilament light only in Alzheimer’s disease but not in other neurodegenerative diseases. Across cohorts, plasma/serum brain-derived tau was associated with CSF and plasma AT(N) biomarkers and cognitive function.

Brain-derived tau is a novel blood-based biomarker that outperforms total plasma and, in contrast to neurofilament light, shows specificity for Alzheimer’s disease-type neurodegeneration. Thus, brain-derived tau shows potential to complete the AT(N) scheme in blood, and would be useful for evaluating AD-dependent neurodegenerative processes for clinical and research purposes.

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