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

Sci Rep. 2020 Jul 8;10(1):11233. doi: 10.1038/s41598-020-68045-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Cerebellar Cortex / diagnostic imaging
  • Cerebellar Cortex / pathology*
  • Disease Models, Animal
  • Female
  • Humans
  • Imaging, Three-Dimensional*
  • Male
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid / diagnosis*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / pathology
  • Presenilin-1 / genetics
  • Radiography
  • Synchrotrons
  • Tomography, X-Ray Computed / instrumentation
  • Tomography, X-Ray Computed / methods

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • presenilin 1, mouse