Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
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Abstract Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood–brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer’s disease. Here, we used focused ultrasound to open the blood–brain barrier in five patients with early to moderate Alzheimer’s disease in a phase I safety trial. In all patients, the blood–brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood–brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using [ 18 F]-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer’s disease.
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A proof of concept study in five Alzheimer's disease patients demonstrated safe and temporary opening of the blood-brain barrier in the white matter of the superficial dorsolateral prefrontal cortex.
“A proof of concept study in five AD patients demonstrated safe and temporary opening of the BBB in the white matter of the superficial dorsolateral prefrontal cortex (11).”
From Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound. (2020) · cites this paper as [11]
This method is safe, reversible, repeatable, and non-invasive for access across the BBB, and promising for AD patients.
“This method is presented as a safe, reversible, repeatable, and non-invasive method for access across the BBB, and thus, it is a promising method for patients with AD [259,260,261].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [260]
In Alzheimer's disease patients, LIFU with injected microbubbles transiently opened the blood-brain barrier in a targeted, noninvasive, safe, and reversible way.
“the application of LIFU, coupled with injected microbubbles, transiently opened the blood brain barrier in a targeted, noninvasive, safe, and reversible manner [68].”
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- Authors
- Lipsman, N., Meng, Y., Bethune, A. J., Huang, Y., Lam, B., Masellis, M., Herrmann, N., Heyn, C., Aubert, I., Boutet, A., Smith, G. S., Hynynen, K., & Black, S. E.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- Johns Hopkins University (US)
- Corresponding author
- Lipsman, Nir
- ORCID
- Venue
- Nature Communications
- Published
- 2018-07-25
- Volume
- 9
- Issue
- 1
- Pages
- 2336-2336
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6060168
- OpenAlex
- W2807207060
- Cited by
- 950
- References
- 39
- Citations by year
- 2026: 93 · 2025: 105 · 2024: 114 · 2023: 140 · 2022: 120 · 2021: 143 · 2020: 120 · 2019: 82 · 2018: 31 · 2012: 1
- FWCI
- 37.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Focused Ultrasound Foundation
- Sunnybrook Research Institute
- Sunnybrook Foundation
- University of Toronto
- National Institute of Biomedical Imaging and Bioengineering (R01EB003268)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Alzheimer's disease, blood-brain barrier opening, MR-guided focused ultrasound, microbubbles, amyloid-beta, tau pathology, 18F-florbetaben PET, amyloid deposition, brain drug delivery, feasibility and safety
- MeSH terms
- Positron Emission Tomography Computed Tomography, Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Biological Transport, Blood-Brain Barrier, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Psychometrics, Stilbenes, Ultrasonography, Amyloid beta-Peptides, Microbubbles
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