Several progressive neurodegenerative disorders, including Alzheimer’s disease, are defined by having tau proteins in the brain. Researchers are seeking to identify the mechanisms behind these tau proteins to develop treatments, however, their efforts to detect biomarkers in blood has been hampered by the protective blood-brain barrier.
At Washington University in St. Louis, new research from the lab of Hong Chen, PhD, associate professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology in the School of Medicine, and collaborators found that using focused-ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker into the blood than without the intervention. This noninvasive method could facilitate diagnosis of neurodegenerative disorders, the researchers said.
The method, known as sonobiopsy, uses focused ultrasound to target a precise location in the brain. Once located, the researchers inject microbubbles into the blood that travel to the ultrasound-targeted tissue and pulsate, which safely opens the blood-brain barrier. The temporary openings allow biomarkers, such as tau proteins and neurofilament light chain protein (NfL), both indicative of neurodegenerative disorders, to pass through the blood-brain barrier and release into the blood.
Chen teamed with co-senior author Arash Nazeri, MD, an assistant professor of radiology at the School of Medicine’s Mallinckrodt Institute of Radiology (MIR). They collaborated with Tammie LS Benzinger, MD, PhD, a professor of radiology at MIR and a professor of neurological surgery and of biology and biological sciences; Eric Leuthardt, MD, a professor of neurosurgery at the School of Medicine and of biomedical engineering at McKelvey Engineering; as well as first author Christopher Pham Pacia, who earned a doctorate in biomedical engineering from Washington University earlier this year; Jinyun Yuan, a research scientist in Chen’s lab; and Yimei Yue, a research technician in Chen’s lab.
Results of the work, the first to open the door for noninvasive and targeted diagnosis and monitoring of neurodegenerative disorders with focused-ultrasound-mediated liquid biopsy, are published in Radiology Jan. 31.