Related Experiment Video
Updated: Aug 12, 2025
An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model
Christopher Pham Pacia1, Jinyun Yuan1, Yimei Yue1
1From the Department of Biomedical Engineering, Washington University in St Louis, 4511 Forest Park Ave, St Louis, MO 63108 (C.P.P., J.Y., Y.Y., E.C.L., H.C.); Department of Neurosurgery (E.C.L.), Mallinckrodt Institute of Radiology (T.L.S.B., A.N.), and Department of Radiation Oncology (H.C.), Washington University School of Medicine, St Louis, Mo.
Focused ultrasound liquid biopsy (sonobiopsy) successfully increased detection of tau protein and neurofilament light chain in the blood of mice with tauopathy. This novel technique shows promise for diagnosing neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Medical Imaging
Background:
- Neurodegenerative disorders, such as Alzheimer disease, are characterized by tau protein deposition and are collectively termed tauopathies.
- Identifying molecular drivers is crucial for targeted treatment, but the blood-brain barrier limits current biomarker analysis.
- Advances in fluid biomarker detection are needed to overcome these diagnostic challenges.
Purpose of the Study:
- To assess the feasibility and safety of focused ultrasound-mediated liquid biopsy (sonobiopsy).
- To detect brain-derived protein biomarkers, specifically phosphorylated tau (p-tau) and neurofilament light chain (NfL), in a mouse model of tauopathy.
- To evaluate sonobiopsy's potential for diagnosing neurodegenerative disorders.
Main Methods:
- Sonobiopsy involved sonicating the cerebral hemisphere or specific regions (hippocampus, cerebral cortex) in PS19 transgenic mice and wild-type controls.
- Plasma levels of p-tau species and NfL were measured before and after sonication.
- Histologic analysis was performed to assess potential tissue damage.
Main Results:
- Sonobiopsy significantly increased plasma p-tau species levels in 2-month-old mice compared to conventional methods.
- Spatially targeted sonobiopsy in 6-month-old mice led to a 2.3-fold increase in plasma NfL levels (P < .001).
- Optimized sonobiopsy parameters showed no significant microhemorrhage, indicating safety.
Conclusions:
- Sonobiopsy is a feasible technique for releasing brain-derived biomarkers like p-tau and NfL into circulation.
- This method holds potential for improved diagnosis of neurodegenerative diseases by overcoming blood-brain barrier limitations.
- Further research may establish sonobiopsy as a valuable tool in clinical practice.
