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Développement et évaluation d'agents de contraste pour détecter la maladie d'Alzheimer par IRM : coloration par le Gadolinium et nanocorps ciblant les protéines Aβ et Tau

Clémence Dudeffant 1
1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
MIRCEN - Service MIRCEN : DRF/JACOB, CNRS - Centre National de la Recherche Scientifique : UMR 9199
Abstract : Magnetic resonance imaging (MRI) has become a key tool for both clinical and preclinical research. Developing innovative neuroimaging techniques specifically designed for small animal models is therefore crucial to validate biological hypotheses and screen new drugs. Amyloid plaques and neurofibrillary tangles are the major lesions characterizing Alzheimer’s disease (AD) and intensive research has been carried out in order to enable the accurate detection of amyloid plaques using high-field MRI. However, only a small portion of plaques are spontaneously detected by MRI and no method is so far available for neurofibrillary tangles imaging. Here, we develop two contrast-enhanced MRI techniques to improve amyloid plaques detection using high-field MRI. The first part of this work focuses on Gadolinium-Staining for amyloid plaques detection by MRI. We performed a comparative study between mice model of amyloi-dosis and non-human primate models, which al-lowed us to gain a better understanding of the origin of the contrast induced by amyloid plaques when performing contrast-enhanced MRI. We also showed for the first time that Gd-stained MRI is able to detect amyloid plaques in human-AD brain tis-sues. The second part of this manuscript describes two novel single-domain antibodies (VHHs or nano-bodies) that are able to specifically recognize and bind amyloid plaques or neurofibrillary tangles. The detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of the blood-brain barrier. Interestingly, VHH exhibiting a basic isoelectric point are able to transmigrate across the blood-brain barrier, thus making them promising tools for in vivo imaging of AD’s lesion at high-field MR.
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https://tel.archives-ouvertes.fr/tel-01908585
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Submitted on : Tuesday, October 30, 2018 - 12:13:06 PM
Last modification on : Monday, July 27, 2020 - 3:02:36 AM

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  • HAL Id : tel-01908585, version 1

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Clémence Dudeffant. Développement et évaluation d'agents de contraste pour détecter la maladie d'Alzheimer par IRM : coloration par le Gadolinium et nanocorps ciblant les protéines Aβ et Tau. Neurosciences [q-bio.NC]. Université Paris Saclay (COmUE), 2018. Français. ⟨NNT : 2018SACLS281⟩. ⟨tel-01908585⟩

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