Amyloid-β plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound
Open accessAbstract
Noninvasive, targeted drug delivery to the brain can be achieved using transcranial focused ultrasound (FUS), which transiently increases the permeability of the blood-brain barrier (BBB) for localized delivery of therapeutics from the blood to the brain. Previously, we have demonstrated that FUS can deliver intravenously-administered antibodies to the brain of a mouse model of Alzheimer's disease (AD) and rapidly reduce plaques composed of amyloid-β peptides (Aβ). Here, we investigated two potential effects of transcranial FUS itself that could contribute to a reduction of plaque pathology, namely the delivery of endogenous antibodies to the brain and the activation of glial cells. We demonstrate that transcranial FUS application leads to a significant reduction in plaque burden four days after a single treatment in the TgCRND8 mouse model of AD and that endogenous antibodies are found bound to Aβ plaques. Immunohistochemical and western blot analyses showed an increase in endogenous immunoglobulins within the FUS-targeted cortex. Subsequently, microglia and astrocytes in FUS-treated cortical regions show signs of activation through increases in protein expression and changes in glial size, without changes in glial cell numbers. Enhanced activation of glia correlated with increased internalization of Aβ in microglia and astrocytes. Together these data demonstrate that FUS improved the bioavailability of endogenous antibodies and led to a temporal activation of glial cells, providing evidence towards antibody- and glia-dependent mechanisms of FUS-mediated plaque reduction.
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Focused ultrasound enables targeted noninvasive delivery of genetic vectors and cells.
“Additionally, this technology enables targeted noninvasive delivery of genetic vectors and cells (6, 8–10).”
From Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound. (2020) · cites this paper as [8]
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- Authors
- Jordão, J. F., Thévenot, E., Markham-Coultes, K., Scarcelli, T., Weng, Y.-Q., Xhima, K., O'Reilly, M., Huang, Y., McLaurin, J., Hynynen, K., & Aubert, I.
- Affiliations
- University of Toronto (CA)
- Sunnybrook Research Institute (CA)
- Corresponding author
- Hynynen, Kullervo
- Aubert, Isabelle
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 248
- Pages
- 16-29
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC4000699
- OpenAlex
- W2108277337
- Cited by
- 326
- References
- 62
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 21 · 2023: 35 · 2022: 35 · 2021: 37 · 2020: 34 · 2019: 29 · 2018: 29 · 2017: 22 · 2016: 16 · 2015: 18 · 2014: 11 · 2013: 1
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ontario Mental Health Foundation
- National Institutes of Health (EB003268)
- Canadian Institutes of Health Research (FRN 93603, FRN 10246)
- 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
- transcranial focused ultrasound, amyloid plaques, Alzheimer's disease, endogenous antibodies, blood-brain barrier permeability, glial activation, microglia, astrocytes, TgCRND8 mice
- MeSH terms
- Alzheimer Disease, Animals, Blood-Brain Barrier, Brain, Female, Immunoglobulin G, Immunoglobulin M, Male, Mice, Transgenic, Neuroglia, Ultrasonography, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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