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ZENODO
Article . 2016
License: CC BY
Data sources: ZENODO
Journal of Alzheimer s Disease
Article . 2016 . Peer-reviewed
Data sources: Crossref
Journal of Alzheimer s Disease
Article . 2016
Data sources: mEDRA
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Monitoring Blood-Brain Barrier Integrity Following Amyloid-β Immunotherapy Using Gadolinium-Enhanced MRI in a PDAPP Mouse Model

Authors: Blockx, Ines; Einstein, Steve; Guns, Pieter-Jan; Van Audekerke, Johan; Guglielmetti, Caroline; Zago, Wagner; Roose, Dimitri; +3 Authors

Monitoring Blood-Brain Barrier Integrity Following Amyloid-β Immunotherapy Using Gadolinium-Enhanced MRI in a PDAPP Mouse Model

Abstract

Background: Amyloid-related imaging abnormalities (ARIA) have been reported with some anti-amyloid-β (Aβ) immunotherapy trials. They are detected with magnetic resonance imaging (MRI) and thought to represent transient accumulation of fluid/edema (ARIA-E) or microhemorrhages (ARIA-H). Although the clinical significance and pathophysiology are unknown, it has been proposed that anti-Aβimmunotherapy may affect blood-brain barrier (BBB) integrity. Objective: To examine vascular integrity in aged (12–16 months) PDAPP and wild type mice (WT), we performed a series of longitudinal in vivo MRI studies. Methods: Mice were treated on a weekly basis using anti-Aβimmunotherapy (3D6) and follow up was done longitudinally from 1–12 weeks after treatment. BBB-integrity was assessed using both visual assessment of T1-weighted scans and repeated T1 mapping in combination with gadolinium (Gd-DOTA). Results: A subset of 3D6 treated PDAPP mice displayed numerous BBB disruptions, whereas WT and saline-treated PDAPP mice showed intact BBB integrity under the conditions tested. In addition, the contrast induced decrease in T1 value was observed in the meningeal and midline area. BBB disruption events occurred early during treatment (between 1 and 5 weeks), were transient, and resolved quickly. Finally, BBB-leakages associated with microhemorrhages were confirmed by Perls’Prussian blue histopathological analysis. Conclusion: Our preclinical findings support the hypothesis that 3D6 leads to transient leakage from amyloid-positive vessels. The current study has provided valuable insights on the time course of vascular alterations during immunization treatment and supports further research in relation to the nature of ARIA and the utility of in vivo repeated T1 MRI as a translational tool.

Country
Belgium
Keywords

neuroimaging, Amyloid beta-Peptides, Gadolinium, Mice, Transgenic, blood-brain barrier, Magnetic Resonance Imaging, Amyloid beta-Protein Precursor, Disease Models, Animal, Mice, transgenic mouse model, Alzheimer Disease, Blood-Brain Barrier, amyloid-related imaging abnormalities, magnetic resonance imaging, Animals, Female, immunotherapy, Human medicine, Immunotherapy, Alzheimer’s disease

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
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18
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