β-Amyloid Plaque Reduction in the Hippocampus After Focused Ultrasound-Induced Blood–Brain Barrier Opening in Alzheimer’s Disease
Open accessAbstract
The blood-brain barrier (BBB) limits therapeutic delivery in Alzheimer’s disease (AD) and other neurological disorders. Animal models have demonstrated safe BBB opening and reduction in β-amyloid plaque with focused ultrasound (FUS). We recently demonstrated the feasibility, safety, and reversibility of FUS induced BBB opening in the hippocampus and entorhinal cortex in 6 participants with early AD. We now report the effect of BBB opening with FUS treatment on β-amyloid plaque. Six participants underwent 18F-Florbetaben PET scan at baseline and one week after the completion of the third FUS treatment (60 days interval). PET analysis comparing the hippocampus and entorhinal cortex in the treated and untreated hemispheres revealed a decrease in the ratio of 18F-Florbetaben ligand binding. The standard uptake value ratios (SUVr) reduction ranged from 2.7-10% with an average of 5.05% (+/-2.76) suggesting a decrease in β-amyloid plaque.
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Cites
Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound.
Rezai, A. R., Ranjan, M., D’Haese, P.-F., Haut, M. W., Carpenter, J., Najib, U., Mehta, R. I., Chazen, J. L., Zibly, Z., Yates, J. R., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002571117 · Cited by 365 · cited 1× · see citing works
“Pre-treatment MRI was used to segment the hippocampi and EC using a non-linear atlas-based algorithm (Rohde et al., 2003; Lavely et al., 2004; Chakravorti et al., 2019).”
MethodSelf-citationBurgess, A., Dubey, S., Yeung, S., Hough, O., Eterman, N., Aubert, I., & Hynynen, K. (2014) · Radiology · doi:10.1148/radiol.14140245 · Cited by 286 · see citing works
Chakravorti, S., Jermakowicz, W. J., Wu, C., Li, R., Wirz Gonzalez, R., Dawant, B. M., & D'Haese, P.-F. (2019) · Medical Imaging 2019: Image-Guided Procedures, Robotic Interventions, and Modeling · doi:10.1117/12.2512587 · Cited by 3 · see citing works
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Dysfunction of the blood–brain barrier in Alzheimer's disease: Evidence from human studies
Kurz, C., Walker, L., Rauchmann, B., & Perneczky, R. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12782 · Cited by 183 · see citing works
“on PET after sonication was also shown, but cognitive outcomes were not reported.(92,93,95)”
- Authors
- D’Haese, P.-F., Ranjan, M., Song, A., Haut, M. W., Carpenter, J., Dieb, G., Najib, U., Wang, P., Mehta, R. I., Chazen, J. L., Hodder, S., Claassen, D., Kaplitt, M., & Rezai, A. R.
- Affiliations
- West Virginia University (US)
- Vanderbilt University (US)
- Weill Cornell Medicine (US)
- Corresponding author
- D’Haese, Pierre-François
- ORCID
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2020-10-07
- Volume
- 14
- Pages
- 593672-593672
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC7575813
- OpenAlex
- W3092195828
- Cited by
- 94
- References
- 3
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 15 · 2023: 20 · 2022: 22 · 2021: 15
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- West Virginia University
- National Institute of General Medical Sciences (U54GM104942)
- 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, amyloid plaques, Alzheimer's disease, hippocampus, entorhinal cortex, 18F-florbetaben PET, amyloid imaging, early Alzheimer's disease, transcranial ultrasound therapy
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