Dataset Information

Assessment of plaque morphology in Alzheimer's mouse cerebellum using three-dimensional X-ray phase-based virtual histology.

ABSTRACT: Visualization and characterization of [Formula: see text]-amyloid deposits is a fundamental task in pre-clinical study of Alzheimer's disease (AD) to assess its evolution and monitor the efficiency of new therapeutic strategies. While the cerebellum is one of the brain areas most underestimated in the context of AD, renewed interest in cerebellar lesions has recently arisen as they may link to motor and cognitive alterations. Thus, we quantitatively investigated three-dimensional plaque morphology in the cerebellum in APP/PS1 transgenic mouse, as a model of AD. In order to obtain a complete high-resolution three-dimensional view of the investigated tissue, we exploited synchrotron X-ray phase contrast tomography (XPCT), providing virtual slices with histology-matching resolution. We found the formation of plaques elongated in shape, and with a specific orientation in space depending on the investigated region of the cerebellar cortex. Remarkably, a similar shape is observed in human cerebellum from demented patients. Our findings demonstrate the capability of XPCT in volumetric quantification, supporting the current knowledge about plaque morphology in the cerebellum and the fundamental role of the surrounding tissue in driving their evolution. A good correlation with the human neuropathology is also reported.

SUBMITTER: Massimi L

PROVIDER: S-EPMC7343834 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Assessment of plaque morphology in Alzheimer's mouse cerebellum using three-dimensional X-ray phase-based virtual histology.

Massimi Lorenzo L Pieroni Nicola N Maugeri Laura L Fratini Michela M Brun Francesco F Bukreeva Inna I Santamaria Giulia G Medici Valentina V Poloni Tino Emanuele TE Balducci Claudia C Cedola Alessia A

Scientific reports 20200708 1

Visualization and characterization of [Formula: see text]-amyloid deposits is a fundamental task in pre-clinical study of Alzheimer's disease (AD) to assess its evolution and monitor the efficiency of new therapeutic strategies. While the cerebellum is one of the brain areas most underestimated in the context of AD, renewed interest in cerebellar lesions has recently arisen as they may link to motor and cognitive alterations. Thus, we quantitatively investigated three-dimensional plaque morpholo ...[more]

PMID: 32641715

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Project description:RationaleRemodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms.ObjectiveWe used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models.Methods and resultsAdipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated.ConclusionsWe present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume. Visual Overview: An online visual overview is available for this article.

Dataset Information

Assessment of plaque morphology in Alzheimer's mouse cerebellum using three-dimensional X-ray phase-based virtual histology.

Publications

Assessment of plaque morphology in Alzheimer's mouse cerebellum using three-dimensional X-ray phase-based virtual histology.

Similar Datasets

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