A Tau-Based Blood Biomarker of Alzheimer's Disease
The primary approach to assessing neurodegeneration presently involves comparatively expensive imaging technologies. Better, less onerous ways to determine the early onset and later progression of Alzheimer's disease will hopefully enable greater screening of patients in the earliest stages of the condition, and drive greater efforts to find effective ways to prevent and reverse Alzheimer's disease. Researchers here report on an improvement in the assessment of tau protein that finds its way into the bloodstream from the brain, making it a viable biomarker for Alzheimer's disease, where in the past it was difficult to establish a correlation.
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). Current blood diagnostic methods can accurately detect abnormalities in plasma amyloid beta and the phosphorylated form of tau, but the biggest hurdle 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. Researchers have now developed a technique to selectively detect BD-tau while avoiding free-floating "big tau" proteins produced by cells outside the brain, however.
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.
Link: https://www.upmc.com/media/news/122722-alzheimers-neurodegeneration