Abstract
Visualization and characterization of beta-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.
Highlights
Visualization and characterization of β-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
Inspection of X-ray phase contrast tomography (XPCT) slices reveals that plaques are concentrated in molecular layer while they are not observed in others layers of the cerebellar cortex
In hemisphere they are oriented normal to transverse plane following the direction of cerebellar cortex, whereas in the vermis they are oriented normal to the sagittal plane forming aligned clusters
Summary
Visualization and characterization of β-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. In order to obtain a complete highresolution three-dimensional view of the investigated tissue, we exploited synchrotron X-ray phase contrast tomography (XPCT), providing virtual slices with histology-matching resolution. Several transgenic mouse models have been developed in order to mimic AD pathology and facilitate the investigation of pathological mechanisms and therapeutic efficacy These models are characterized by the presence of AD-related human mutations in the APP gene alone or in combination with mutations on the presenilin 1 or 2 genes, all involved in the release of the β A peptide. The cerebellar cortex presents a highly ordered structure both at macroscopic examination as well as at cellular level, providing an interesting base to explore the properties of plaques as a function of the surrounding tissue, and of the cytoarchitecture of that specific brain area. A striking similarity with the plaques of the human cerebellum is found, suggesting that amyloid aggregates in humans develop through similar processes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
