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Barbone, G.E.* ; Bravin, A.* ; Mittone, A.* ; Pacureanu, A.* ; Mascio, G.* ; Di Pietro, P.* ; Kraiger, M. ; Eckermann, M.* ; Romano, M.* ; Hrabě de Angelis, M. ; Cloetens, P.* ; Bruno, V.* ; Battaglia, G.* ; Coan, P.*

X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer’s disease.

Eur. J. Nucl. Med. Mol. Imaging 49, 4338-4357 (2022)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Purpose: Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia. In deep neuronal populations in the brain of aged wild-type and of 3xTgAD mice (a triply-transgenic model of Alzheimer’s disease), we quantified intracellular hyperdensity, a manifestation of aging or neurodegeneration. Results: In 3xTgAD mice, the observed hyperdensity was identified as amyloid-β and hyper-phosphorylated tau protein deposits with calcium and iron involvement, by correlating the X-PCI-CT data to immunohistochemistry, X-ray fluorescence microscopy, high-field MRI, and TEM. As a proof-of-concept, X-PCI-CT was used to analyze hippocampal and cortical brain regions of 3xTgAD mice treated with LY379268, selective agonist of group II metabotropic glutamate receptors (mGlu2/3 receptors). Chronic pharmacologic activation of mGlu2/3 receptors significantly reduced the hyperdensity particle load in the ventral cortical regions of 3xTgAD mice, suggesting a neuroprotective effect with locoregional efficacy. Conclusions: This multiscale micro-to-nano 3D imaging method based on X-PCI-CT enabled identification and quantification of cellular and sub-cellular aging and neurodegeneration in deep neuronal and glial cell populations in a transgenic model of Alzheimer’s disease. This approach quantified the localized and intracellular neuroprotective effects of pharmacological activation of mGlu2/3 receptors.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Alzheimer’s Disease ; Metabotropic Glutamate Receptors ; Micro-ct ; Nano-imaging ; Neuro-radiology ; Neurodegeneration
ISSN (print) / ISBN 1619-7070
e-ISSN 1432-105X
Journal European Journal of Nuclear Medicine and Molecular Imaging
Quellenangaben Volume: 49, Issue: 13, Pages: 4338-4357 Article Number: , Supplement: ,
Publisher Springer
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Grants Région Auvergne-Rhône-Alpes
Fondation pour la Recherche Medicale
Ministero della Salute
Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
European Cooperation in Science and Technology
International Max Plank Research School of Advanced Photon Science
GIS-IBISA
Fonds FEDER
DFG Cluster of Excellence)—Munich Center for Advanced Photonics