Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
Open accessAbstract
Background: Focused ultrasound (FUS)-mediated blood–brain barrier (BBB) opening has shown efficacy in removal of amyloid plaque and improvement of cognitive functions in preclinical studies, but this is rarely reported in clinical studies. This study was conducted to evaluate the safety, feasibility and potential benefits of repeated extensive BBB opening. Methods: In this open-label, prospective study, six patients with Alzheimer’s disease (AD) were enrolled at Severance Hospital in Korea between August 2020 and September 2020. Five of them completed the study. FUS-mediated BBB opening, targeting the bilateral frontal lobe regions over 20 cm 3 , was performed twice at three-month intervals. Magnetic resonance imaging, 18 F-Florbetaben (FBB) positron emission tomography, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) and comprehensive neuropsychological tests were performed before and after the procedures. Results: FUS targeted a mean volume of 21.1 ± 2.7 cm 3 and BBB opening was confirmed at 95.7% ± 9.4% of the targeted volume. The frontal-to-other cortical region FBB standardized uptake value ratio at 3 months after the procedure showed a slight decrease, which was statistically significant, compared to the pre-procedure value (− 1.6%, 0.986 vs 1.002, P = 0.043). The CGA-NPI score at 2 weeks after the second procedure significantly decreased compared to baseline (2.2 ± 3.0 vs 8.6 ± 6.0, P = 0.042), but recovered after 3 months (5.2 ± 5.8 vs 8.6 ± 6.0, P = 0.89). No adverse effects were observed. Conclusions: The repeated and extensive BBB opening in the frontal lobe is safe and feasible for patients with AD. In addition, the BBB opening is potentially beneficial for amyloid removal in AD patients.
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- Authors
- Park, S. H., Baik, K., Jeon, S., Chang, W. S., Ye, B. S., & Chang, J. W.
- Affiliations
- Yonsei University (KR)
- Corresponding author
- Chang, Won Seok
- Ye, Byoung Seok
- Chang, Jin Woo
- Venue
- Translational Neurodegeneration
- Published
- 2021-11-05
- Volume
- 10
- Issue
- 1
- Pages
- 44-44
- ISSN
- 2047-9158 (ISSN-L)
- PMC
- PMC8570037
- OpenAlex
- W3210405129
- Cited by
- 95
- References
- 4
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 24 · 2023: 16 · 2022: 22 · 2021: 1
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- ministry of education, science and technology (2016M3C7A1914123)
- 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
- focused ultrasound, blood-brain barrier opening, Alzheimer's disease, amyloid PET, 18F-florbetaben, frontal lobe, neuropsychiatric symptoms, treatment safety and feasibility
- MeSH terms
- Alzheimer Disease, Blood-Brain Barrier, Humans, Prospective Studies, Tomography, X-Ray Computed, Plaque, Amyloid
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