Blood–brain barrier opening of the default mode network in Alzheimer’s disease with magnetic resonance-guided focused ultrasound
Open accessAbstract
The blood–brain barrier (BBB) protects the brain but is also an important obstacle for the effective delivery of therapeutics in Alzheimer’s disease and other neurodegenerative disorders. Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt the BBB. However, treatment of diffuse regions across the brain along with the effect on Alzheimer’s disease relevant pathology need to be better characterized. This study is an open-labelled single-arm trial (NCT03739905) to investigate the feasibility of modulating BBB permeability in the default mode network and the impact on cognition, amyloid and tau pathology as well as BBB integrity. Nine participants [mean age 70.2 ± 7.2 years, mean Mini-Mental State Examination (MMSE) 21.9] underwent three biweekly procedures with follow-up visits up to 6 months. The BBB permeability of the bilateral hippocampi, anterior cingulate cortex and precuneus was transiently increased without grade 3 or higher adverse events. Participants did not experience worsening trajectory of cognitive decline (ADAS-cog11, MMSE). Whole brain vertex-based analysis of the 18F-florbetaben PET imaging demonstrated clusters of modest SUVR reduction in the right parahippocampal and inferior temporal lobe. However, CSF and blood biomarkers did not demonstrate any amelioration of Alzheimer’s disease pathology (P-tau181, amyloid-β42/40 ratio), nor did it show persistent BBB dysfunction (plasma PDGFRbeta and CSF-to-plasma albumin ratio). This study provides neuroimaging and fluid biomarker data to characterize the safety profile of MRgFUS BBB modulation in neurodegeneration as a potential strategy for enhanced therapeutic delivery.
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Cites
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study
Sabri, O., Sabbagh, M. N., Seibyl, J., Barthel, H., Akatsu, H., Ouchi, Y., Senda, K., Murayama, S., Ishii, K., Takao, M., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.004 · Cited by 602 · see citing works
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 · see citing works
A resurrection of aducanumab for Alzheimer's disease
Schneider, L. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30480-6 · Cited by 286 · see citing works
Burgess, 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
Self-citationZetterberg, H. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.90 · Cited by 234 · see citing works
Self-citationNisbet, R. M., Van der Jeugd, A., Leinenga, G., Evans, H. T., Janowicz, P. W., & Götz, J. (2017) · Brain · doi:10.1093/brain/awx052 · Cited by 187 · see citing works
Glymphatics visualization after focused ultrasound-induced blood-brain barrier opening in humans
Meng, Y., Abrahao, A., Heyn, C. C., Bethune, A. J., Huang, Y., Pople, C. B., Aubert, I., Hamani, C., Zinman, L., Hynynen, K., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25604 · Cited by 114 · see citing works
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- Authors
- Meng, Y., Goubran, M., Rabin, J. S., McSweeney, M., Ottoy, J., Pople, C. B., Huang, Y., Storace, A., Ozzoude, M., Bethune, A., Lam, B., Swardfager, W., Heyn, C., Abrahao, A., Davidson, B., Hamani, C., Aubert, I., Zetterberg, H., Ashton, N. J., Karikari, T. K., Blennow, K., Black, S. E., Hynynen, K., & Lipsman, N.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada
- Sahlgrenska University Hospital (SE)
- King's College London (GB)
- University of Pittsburgh (US)
- Corresponding author
- Lipsman, Nir
- ORCID
- Meng, Ying
- Goubran, Maged
- Rabin, Jennifer S
- Ottoy, Julie
- Pople, Christopher B
- Huang, Yuexi
- Ozzoude, Miracle
- Bethune, Allison
- Lam, Benjamin
- Swardfager, Walter
- Abrahao, Agessandro
- Davidson, Benjamin
- Hamani, Clement
- Aubert, Isabelle
- Zetterberg, Henrik
- Ashton, Nicholas J
- Karikari, Thomas K
- Blennow, Kaj
- Black, Sandra E
- Hynynen, Kullervo
- Lipsman, Nir
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-01-25
- Volume
- 146
- Issue
- 3
- Pages
- 865-872
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC10226733
- OpenAlex
- W4317915794
- Cited by
- 83
- References
- 10
- Citations by year
- 2026: 25 · 2025: 28 · 2024: 26 · 2023: 4
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Weston Brain Institute
- Focused Ultrasound Foundation
- Harquail Centre for Neuromodulation
- Sunnybrook Foundation
- Swedish Research Council (#2017-00915, #2018-02532)
- Swedish Alzheimer Foundation (#AF-742881, #FO2017-0243, #ALFGBG-715986)
- European Research Council (#681712, #ALFGBG-720931)
- Swedish State Support for Clinical Research (#ALFGBG-720931)
- Alzheimer Drug Discovery Foundation (#201809-2016862)
- UCL
- Canadian Institute of Health Research (154272)
- National Institute of Biomedical Imaging and Bioengineering
- National Institutes of Health (RO1-EB003268)
- Temerty Chair in Focused Ultrasound Research
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, blood-brain barrier opening, MR-guided focused ultrasound, default mode network, blood-brain barrier permeability, amyloid-beta, tau pathology, 18F-florbetaben PET, PDGFRβ, cognitive decline, hippocampus, anterior cingulate cortex, precuneus, brain drug delivery
- MeSH terms
- Default Mode Network, Aged, Alzheimer Disease, Blood-Brain Barrier, Humans, Middle Aged, Magnetic Resonance Spectroscopy, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction
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