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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 13/2022

Open Access 19-07-2022 | Alzheimer's Disease | Original Article

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

Authors: Giacomo E. Barbone, Alberto Bravin, Alberto Mittone, Alexandra Pacureanu, Giada Mascio, Paola Di Pietro, Markus J. Kraiger, Marina Eckermann, Mariele Romano, Martin Hrabě de Angelis, Peter Cloetens, Valeria Bruno, Giuseppe Battaglia, Paola Coan

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 13/2022

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Abstract

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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Metadata
Title
X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer’s disease
Authors
Giacomo E. Barbone
Alberto Bravin
Alberto Mittone
Alexandra Pacureanu
Giada Mascio
Paola Di Pietro
Markus J. Kraiger
Marina Eckermann
Mariele Romano
Martin Hrabě de Angelis
Peter Cloetens
Valeria Bruno
Giuseppe Battaglia
Paola Coan
Publication date
19-07-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 13/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05896-5

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