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Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model
Pacia CP, Yuan J, Yue Y, Leuthardt EC, Benzinger TLS, Nazeri A, Chen H.. Radiology, 2023-01-31
Topic: Brain proteins, microglia and lab models
Background Neurodegenerative disorders (such as Alzheimer disease) characterized by the deposition of various pathogenic forms of tau protein in the brain are collectively referred to as tauopathies. Identification of the molecular drivers and pathways of neurodegeneration is critical to individualized targeted treatment of these disorders. However, despite important advances in fluid biomarker detection, characterization of these molecular subtypes is limited by the blood-brain barrier. Purpose To evaluate the feasibility and safety of focused ultrasound-mediated liquid biopsy (sonobiopsy) in the detection of brain-derived protein biomarkers in a transgenic mouse model of tauopathy (PS19 mice). Materials and Methods Sonobiopsy was performed by sonicating the cerebral hemisphere in 2-month-old PS19 and wild-type mice, followed by measurement of plasma phosphorylated tau (p-tau) species (30 minutes after sonication in the sonobiopsy group). Next, spatially targeted sonobiopsy was performed by sonicating either the cerebral cortex or the hippocampus in 6-month-old PS19 mice. To detect changes in plasma neurofilament light chain (a biomarker of neurodegeneration) levels, blood samples were collected before and after sonication (15 and 45-60 minutes after sonication). Histologic staining was performed to evaluate tissue damage after sonobiopsy. The Shapiro-Wilk test, unpaired and paired t tests, and the Mann-Whitney U test were used. Results In the 2-month-old mice, sonobiopsy significantly increased the normalized levels of plasma p-tau species compared with the conventional blood-based liquid biopsy (p-tau-181-to-mouse tau [m-tau] ratio: 1.7-fold increase, P = .006; p-tau-231-to-m-tau ratio: 1.4-fold increase, P = .048). In the 6-month-old PS19 mice, spatially targeted sonobiopsy resulted in a 2.3-fold increase in plasma neurofilament light chain after sonication of the hippocampus and cerebral cortex ( P Supplemental material is available for this article. See also the editorial by Fowlkes in this issue.
Key findings
- Results In the 2-month-old mice, sonobiopsy significantly increased the normalized levels of plasma p-tau species compared with the conventional blood-based liquid biopsy (p-tau-181-to-mouse tau [m-tau] ratio: 1.7-fold increase, P = .006; p-tau-231-to-m-tau ratio: 1.4-fold increase, P = .048).
Why it matters
In a mouse model of tauopathy, focused ultrasound briefly raised blood levels of p-tau, suggesting a possible way to detect brain proteins through blood. This is early animal work and does not show any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Radiology) |
| Journal's citation record | 3 / 4 | Radiology: journal h-index 431 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 23 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.6 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hong Chen: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36719290) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 39 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Pacia, C. P., Yuan, J., Yue, Y., Leuthardt, E. C., Benzinger, T. L. S., Nazeri, A., et al. (2023). Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model. Radiology. https://doi.org/10.1148/radiol.220869
Vancouver
Pacia CP, Yuan J, Yue Y, Leuthardt EC, Benzinger TLS, Nazeri A, et al. Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model. Radiology. 2023. doi:10.1148/radiol.220869. PMID: 36719290.
BibTeX
@article{pacia2023-36719290,
author = {Pacia, C. P. and Yuan, J. and Yue, Y. and Leuthardt, E. C. and Benzinger, T. L. S. and Nazeri, A. and Chen, H.},
title = {{Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model}},
journal = {Radiology},
year = {2023},
doi = {10.1148/radiol.220869},
pmid = {36719290},
url = {https://doi.org/10.1148/radiol.220869}
}
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