Focused ultrasound-mediated APOE4 knockdown in mouse brain
Kaiyuan Zheng, Fotios N Tsitsos, Alec J Batts, Robin Ji, Tal Nuriel, Elisa E Konofagou, Kam W Leong. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-07
Topic: Inflammation, microglia and astrocytes
FUS-enhanced delivery of AAV resulted in a 12.6% knockdown of APOE ε4 gene expression in the targeted hippocampus, accompanied by an over 20% decrease in apoE4 protein levels and significant reductions in astrocyte and microglia levels. Our findings demonstrate a noninvasive, targeted approach for APOE ε4 knockdown, highlighting FUS-mediated brain-directed interventions as a promising therapeutic strategy for Alzheimer's disease. HIGHLIGHTS: Focused ultrasound (FUS) enables noninvasive, transient blood-brain barrier (BBB) opening for enhanced adeno-associated virus (AAV) delivery. FUS-mediated gene editing achieves a 12.6% knockdown in APOE ε4 expression within the hippocampus of mouse brain. APOE ε4 knockdown significantly reduces apoE4 protein levels and astrocyte and microglia levels. No detectable gross toxicity was observed following the FUS-mediated gene editing.
Key findings
- FUS-enhanced delivery of AAV resulted in a 12.6% knockdown of APOE ε4 gene expression in the targeted hippocampus, accompanied by an over 20% decrease in apoE4 protein levels and significant reductions in astrocyte and microglia levels.
- Our findings demonstrate a noninvasive, targeted approach for APOE ε4 knockdown, highlighting FUS-mediated brain-directed interventions as a promising therapeutic strategy for Alzheimer's disease.
- HIGHLIGHTS: Focused ultrasound (FUS) enables noninvasive, transient blood-brain barrier (BBB) opening for enhanced adeno-associated virus (AAV) delivery.
- FUS-mediated gene editing achieves a 12.6% knockdown in APOE ε4 expression within the hippocampus of mouse brain.
- APOE ε4 knockdown significantly reduces apoE4 protein levels and astrocyte and microglia levels.
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Study details
- Effect size12.6%
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 28 of the 56 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40665471) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 28 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 28 of the 56 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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Read the original
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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
Zheng, K., Tsitsos, F. N., Batts, A. J., Ji, R., Nuriel, T., Konofagou, E. E., et al. (2025). Focused ultrasound-mediated APOE4 knockdown in mouse brain. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70464
Vancouver
Zheng K, Tsitsos FN, Batts AJ, Ji R, Nuriel T, Konofagou EE, et al. Focused ultrasound-mediated APOE4 knockdown in mouse brain. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70464. PMID: 40665471.
BibTeX
@article{zheng2025-40665471,
author = {Zheng, Kaiyuan and Tsitsos, Fotios N and Batts, Alec J and Ji, Robin and Nuriel, Tal and Konofagou, Elisa E and Leong, Kam W},
title = {{Focused ultrasound-mediated APOE4 knockdown in mouse brain}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70464},
pmid = {40665471},
url = {https://doi.org/10.1002/alz.70464}
}
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