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Unlocking the blood-brain barrier: Can low-intensity focused ultrasound enable effective delivery of anti-amyloid and anti-tau antibodies in Alzheimer's disease?
Desale SH, Doshi PP, Khutale AA, Suresh S.. Ageing research reviews, 2026-09-20
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) remains a major unmet medical challenge despite decades of progress in medicines that target tau and amyloid-β (Aβ) pathology. The clinical benefit of monoclonal antibodies (mAbs) against Aβ is limited, with current data showing only slight slowing of cognitive decline despite encouraging biomarker responses and recent regulatory approval of these drugs. Moreover, their wider clinical use is restricted by dose-dependent toxicities such as amyloid-related imaging abnormalities (ARIA), and by the need for continuous long-term assessment of efficacy and safety in AD patients. The poor penetration of the blood-brain barrier (BBB) by large biologics is a significant but often overlooked factor contributing to this discrepancy. Low-intensity focused ultrasound (LIFU) has emerged as a non-invasive technique for transient localized modification of BBB permeability when paired with intravenously administered microbubbles. This evaluation examines LIFU as a means of delivering anti-tau and anti-amyloid antibodies to AD patients. By integrating data from early-phase clinical research with biological insights, we investigate whether altering the BBB can overcome the pharmacokinetic (PK) limitations of existing immunotherapies. LIFU has biological effects that are critical to the pathophysiology of AD in addition to aiding the mobility of macromolecules, such as enhanced lymphatic clearance and focused neuroimmune activation, which could help treatments based on antibodies. Clinical research to date shows that, in properly chosen AD cohorts, LIFU-mediated BBB opening is practical, reversible, and generally safe; however, there is still a lack of conclusive evidence connecting BBB modulation to elevated intraparenchymal antibody levels or long-term cognitive enhancement. We propose that LIFU should currently be regarded as a promising investigational adjunct to immunotherapy rather than an established therapeutic modality for AD. Biomarker-driven evidence of enhanced cerebral medication distribution and therapeutic effects determines its translational significance; BBB alteration could become a standard Alzheimer's therapeutic strategy if LIFU is successful.
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APA 7th
Desale, S. H., Doshi, P. P., Khutale, A. A., & Suresh, S. (2026). Unlocking the blood-brain barrier: Can low-intensity focused ultrasound enable effective delivery of anti-amyloid and anti-tau antibodies in Alzheimer's disease? Ageing research reviews. https://doi.org/10.1016/j.arr.2026.103379
Vancouver
Desale SH, Doshi PP, Khutale AA, Suresh S. Unlocking the blood-brain barrier: Can low-intensity focused ultrasound enable effective delivery of anti-amyloid and anti-tau antibodies in Alzheimer's disease? Ageing research reviews. 2026. doi:10.1016/j.arr.2026.103379. PMID: 42764107.
BibTeX
@article{desale2026-42764107,
author = {Desale, S. H. and Doshi, P. P. and Khutale, A. A. and Suresh, S.},
title = {{Unlocking the blood-brain barrier: Can low-intensity focused ultrasound enable effective delivery of anti-amyloid and anti-tau antibodies in Alzheimer's disease?}},
journal = {Ageing research reviews},
year = {2026},
doi = {10.1016/j.arr.2026.103379},
pmid = {42764107},
url = {https://doi.org/10.1016/j.arr.2026.103379}
}
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Key findings
- The poor penetration of the blood-brain barrier (BBB) by large biologics is a significant but often overlooked factor contributing to this discrepancy.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 and multi-centre collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Ageing research reviews) |
| 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 | 5 / 5 | 2026 — within 1 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 42764107) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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