Blood-brain barrier opening of the default mode network in Alzheimer's disease with magnetic resonance-guided focused ultrasound.

Humans Middle Aged Aged Alzheimer Disease Blood-Brain Barrier / pathology Default Mode Network / metabolism tau Proteins / metabolism Cognitive Dysfunction / pathology Positron-Emission Tomography / methods Biomarkers Magnetic Resonance Spectroscopy Amyloid beta-Peptides
18F-florbetaben PET Alzheimer’s disease biomarkers blood-brain barrier focused ultrasound

Journal

Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537

Informations de publication

Date de publication:
01 03 2023
Historique:
received: 10 08 2022
revised: 13 10 2022
accepted: 06 11 2022
pmc-release: 25 01 2024
pubmed: 26 1 2023
medline: 4 3 2023
entrez: 25 1 2023
Statut: ppublish

Résumé

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 (NCT04118764) 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.

Identifiants

DOI: 10.1093/brain/awac459 PMID: 36694943 PMC: PMC10226733
pubmed: 36694943
pii: 7000240
doi: 10.1093/brain/awac459
pmc: PMC10226733
doi:

Substances chimiques

tau Proteins 0
Biomarkers 0
Amyloid beta-Peptides 0

Banques de données

ClinicalTrials.gov
['NCT03739905']

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

865-872

Subventions

Organisme : NIBIB NIH HHS
ID : R01 EB003268
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Références

J Neuropathol Exp Neurol. 2012 May;71(5):362-81
pubmed: 22487856
Nat Rev Neurol. 2020 Mar;16(3):137-153
pubmed: 32094487
Transl Neurodegener. 2021 Nov 5;10(1):44
pubmed: 34740367
Nat Commun. 2017 Oct 31;8(1):1214
pubmed: 29089479
PLoS One. 2017 Dec 6;12(12):e0189155
pubmed: 29211812
Neuroimage. 2016 May 15;132:334-343
pubmed: 26915497
Sci Rep. 2018 Sep 19;8(1):14061
pubmed: 30232364
Nat Rev Neurol. 2021 Jan;17(1):7-22
pubmed: 33106619
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42
pubmed: 15070770
Sci Rep. 2019 Jan 23;9(1):321
pubmed: 30674905
Alzheimers Dement. 2015 Aug;11(8):964-74
pubmed: 25824567
Brain Stimul. 2014 Mar-Apr;7(2):304-7
pubmed: 24629831
Nat Commun. 2019 Jun 4;10(1):2353
pubmed: 31164641
Ann Neurol. 2019 Dec;86(6):975-980
pubmed: 31525269
Neuro Oncol. 2021 Oct 1;23(10):1789-1797
pubmed: 33693781
Exp Neurol. 2013 Oct;248:16-29
pubmed: 23707300
Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32691-32700
pubmed: 33288687
PLoS One. 2010 May 11;5(5):e10549
pubmed: 20485502
EMBO Mol Med. 2016 Jun 01;8(6):595-608
pubmed: 27025652
Sci Transl Med. 2021 Oct 13;13(615):eabj4011
pubmed: 34644145
Alzheimers Dement (N Y). 2018 Sep 06;4:575-590
pubmed: 30406177
Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9180-9182
pubmed: 32284421
Neuroimage. 2012 Jul 16;61(4):1402-18
pubmed: 22430496
Nature. 2016 Aug 31;537(7618):50-6
pubmed: 27582220
Nat Commun. 2019 Sep 26;10(1):4373
pubmed: 31558719
Theranostics. 2019 Jul 13;9(18):5396-5411
pubmed: 31410223
Nat Commun. 2018 Jul 25;9(1):2336
pubmed: 30046032
J Nucl Med. 2018 Jul;59(7):1104-1110
pubmed: 29175981
Arch Neurol. 2012 Aug;69(8):1002-10
pubmed: 22473769
Mov Disord. 2022 Oct;37(10):2134-2139
pubmed: 36089809
Neuroimage. 2010 Dec;53(4):1181-96
pubmed: 20637289
Radiology. 2014 Dec;273(3):736-45
pubmed: 25222068
Front Hum Neurosci. 2020 Oct 07;14:593672
pubmed: 33132889
Lancet Neurol. 2020 Feb;19(2):111-112
pubmed: 31978357
Brain. 2017 May 1;140(5):1220-1230
pubmed: 28379300
Neurology. 2016 Aug 2;87(5):539-47
pubmed: 27371494
Anesthesiology. 2016 Feb;124(2):362-8
pubmed: 26575144

Auteurs

Ying Meng (Y)

Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
ORCID: 0000-0003-3180-2404

Maged Goubran (M)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Jennifer S Rabin (JS)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Rehabilitation Sciences Institute, University of Toronto, Toronto, ON M5G 1V7, Canada.
Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON M4N 3M5, Canada.
ORCID: 0000-0003-4754-2221

Melissa McSweeney (M)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Julie Ottoy (J)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
ORCID: 0000-0002-9879-7497

Christopher B Pople (CB)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Yuexi Huang (Y)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Alexandra Storace (A)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Miracle Ozzoude (M)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Allison Bethune (A)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Benjamin Lam (B)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON M4N 3M5, Canada.

Walter Swardfager (W)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Chinthaka Heyn (C)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Agessandro Abrahao (A)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON M4N 3M5, Canada.
ORCID: 0000-0003-1142-2842

Benjamin Davidson (B)

Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Clement Hamani (C)

Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

Isabelle Aubert (I)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
ORCID: 0000-0001-5163-9961

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 413 45 Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK.
UK Dementia Research Institute at UCL, London W1T 7NF, UK.
ORCID: 0000-0003-3930-4354

Nicholas J Ashton (NJ)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London SE5 9RX, UK.
NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London SE5 8AF, UK.

Thomas K Karikari (TK)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
ORCID: 0000-0003-1422-4358

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 413 45 Mölndal, Sweden.

Sandra E Black (SE)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON M4N 3M5, Canada.

Kullervo Hynynen (K)

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Nir Lipsman (N)

Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Blood-brain barrier opening of the default...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Blood-brain barrier opening of the default...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Blood-brain barrier opening of the default...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Blood-brain barrier opening of the default...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Barrière hémato-encéphalique › Blood-brain barrier opening of the default...
questionsmedicales.fr › Système nerveux › Voies nerveuses › Réseau du mode par défaut › Blood-brain barrier opening of the default...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Blood-brain barrier opening of the default...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Blood-brain barrier opening of the default...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Blood-brain barrier opening of the default...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Blood-brain barrier opening of the default...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Spectroscopie par résonance magnétique › Blood-brain barrier opening of the default...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Blood-brain barrier opening of the default...