Researchers at Washington University in St. Louis have developed a technique that can release difficult-to-access biomarker proteins from the brain. At present, the researchers are focused on releasing tau proteins that are implicated in Alzheimer’s disease and other neurodegenerative diseases. These proteins are typically locked behind specialized blood vessels in the brain, otherwise known as the blood-brain barrier, but allowing them to enter the bloodstream could enable clinicians to rapidly and minimally invasively assess their status by analyzing a simple blood sample. This approach involves delivering microbubbles into the bloodstream and then using focused ultrasound to target them as they pass through the blood-brain barrier. The resulting pulsatile action opens temporary pores in the blood vessels, allowing the proteins to escape into the bloodstream.
The brain occupies a privileged position in our skull, with specialized blood vessels protecting it from many of the substances and cells in our bloodstream that can access and affect most other tissues. However, the blood-brain barrier also presents an impediment to substances within the brain, preventing their escape into the bloodstream. This is true of proteins, such as tau proteins that play a role in Alzheimer’s disease, making diagnostic endeavors for neurodegenerative diseases more challenging for clinicians.
This issue has prompted these researchers to apply a method that has previously been explored as a drug delivery approach. However, rather than usinge this method to deliver something through the blood-brain barrier into the brain, these researchers were focused on helping protein biomarkers escape from the brain.
The technique in question involves delivering tiny microbubbles through the bloodstream. Once they reach a target site in the blood vessels of the brain, the researchers switch on a focused ultrasound source. The ultrasound causes the microbubbles to vibrate rapidly and this causes temporary pores to open in the blood-brain barrier, allowing tau proteins to escape into the bloodstream.
So far, the researchers have tested the approach in mice and report that the sonobiopsy method led to a significant increase in the amount of detectable tau protein in the bloodstream. “In our proof-of-concept study, we sought to determine whether sonobiopsy is able to release phosphorylated tau species and NfL into the bloodstream by opening the blood-brain barrier,” said Hong Chen, a researcher involved in the study. “This demonstration showed that sonobiopsy significantly enhanced the release of pTau proteins and a secondary marker of neurodegeneration into the bloodstream for noninvasive diagnosis for neurodegenerative diseases.”
Study in journal Radiology: Focused Ultrasound–mediated Liquid Biopsy in a Tauopathy Mouse Mode