A new blood test has been developed that can track and follow neurodegeneration in Alzheimer’s disease patients.
The new blood test, which can exclude other dementias, has been developed by researchers at the University of Gothenburg, alongside colleagues in Italy and USA.
In recent years, research in this field has largely been focused on developing biomarkers in blood that could help the diagnosis and monitoring of Alzheimer’s disease. Tau, one of the main proteins involved in Alzheimer’s disease pathology, has been heavily researched in the biomarker field.
Tracking neurodegeneration is a challenging process
The emergence of new blood-based phosphorylated tau markers for Alzheimer’s disease has proven that accessible and effective test screening of suspected Alzheimer’s patients is possible. However, even with current technology, measuring brain proteins in blood is very difficult.
Researchers from the University of Gothenburg and their partners developed a novel antibody that can specifically target tau isoforms that originate in the brain. This is achieved by taking advantage of the architectural differences in the structure of tau protein found in the brain versus peripheral sources.
These discoveries enabled the researchers to develop a new blood test that specifically and selectively measures non-phosphorylated 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) assay has demonstrated robust and stable technical performances in blood. There are strong clinical correlations between BD-tau levels in blood and CSF, showing that the assay can be used to measure brain tau. In total, the researchers measured BD-tau levels in blood samples from 609 patients.
In a cohort of patients who had received an autopsy-verified diagnosis, plasma BD-tau showed to be a marker of neurodegeneration that differentiated Alzheimer’s disease from other dementias.
Notably, plasma BD-tau correlated with amyloid plaque and tau tangle loads in the brains of these patients, whereas neurofilament light (NfL) did not. This further shows BD-tau’s specificity to Alzheimer’s disease.
The researchers then studied two separate memory clinic cohorts that included patients who had been diagnosed with Alzheimer’s disease and other dementias or controls. Once again, plasma BD-tau demonstrated high accuracy in differentiating Alzheimer’s disease from other dementias, also outperforming plasma NfL. BD-tau can uniquely reflect the extent of neurodegeneration in patients with Alzheimer’s disease.
Putting the blood tests into practice
A decade ago, the National Institutes on Aging and the Alzheimer’s Association of the USA proposed a new framework to identify and stage the progress of Alzheimer’s disease using biological evidence.
As a result, the AT(N) model was developed, which focuses on biomarkers of amyloid (A), tau (T), and neurodegeneration (N), and it has been authenticated using cerebrospinal fluid (CSF) and neuroimaging biomarkers.
However, it is not possible to fully implement the AT(N) system using blood biomarkers. This is due to the lack of an N marker that shows specificity to Alzheimer pathophysiology. With Plasma BD-tau the AT(N) scheme, as a true neurodegeneration marker that is specific to Alzheimer-type pathology, can be completed.
BD-tau will help researchers to understand neurodegenerative processes in Alzheimer’s disease and examine how they differ from those in other dementias. From a clinical perspective, BD-tau could be used for quick and accessible blood testing to diagnose and monitor disease progression in patients with Alzheimer’s disease.